Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance...Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed t...Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.展开更多
Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores th...Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores the multifaceted roles of macrophage senescence in cancer, and establishes links between senescent macrophages and tumor progression from multiple perspectives, on the basis of the first comprehensive analysis of the molecular mechanisms and pathways involved. By systematically examining the diverse changes in senescent macrophages, this review integrates and analyzes their effects on tumors, thus offering a comprehensive and novel theoretical foundation, and practical insights for cancer treatment. Notably, by integrating current molecular research and therapeutic advancements, we summarize novel therapeutic strategies targeting senescent macrophages, including senolytics, senescence modulators, and cutting-edge immunotherapies, thereby highlighting the potential of senescent macrophages as a therapeutic target and introducing new opportunities for cancer treatment.展开更多
Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An...Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.Results Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate(cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.Conclusions FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.展开更多
Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury.After injury,Schwann cells produce an inflammatory response and secrete various chemokines,inflammatory factors,and some othe...Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury.After injury,Schwann cells produce an inflammatory response and secrete various chemokines,inflammatory factors,and some other cytokines to promote the recruitment and M2 polarization of blood-derived macrophages,enhancing their phagocytotic ability,and thus play an important role in promoting nerve regeneration.Macrophages have also been found to promote vascular regeneration after injury,promote the migration and proliferation of Schwann cells along blood vessels,and facilitate myelination and axon regeneration.Therefore,there is a close interaction between Schwann cells and macrophages during peripheral nerve regeneration,but this has not been systematically summarized.In this review,the mechanisms of action of Schwann cells and macrophages in each other's migration and phenotypic transformation are reviewed from the perspective of each other,to provide directions for research on accelerating nerve injury repair.展开更多
BACKGROUND Tumor-associated macrophages(TAMs)have demonstrated significant potential as a research and treatment approach for hepatocellular carcinoma(HCC).Nevertheless,a comprehensive quantitative analysis of TAMs in...BACKGROUND Tumor-associated macrophages(TAMs)have demonstrated significant potential as a research and treatment approach for hepatocellular carcinoma(HCC).Nevertheless,a comprehensive quantitative analysis of TAMs in HCC remained insufficient.Therefore,the objective of this study was to employ bibliometric methods to investigate the development trends and research frontiers pertaining to this field.AIM To determine the knowledge structure and current research hotspots by bibliometric analysis of scholarly papers pertaining to TAMs in HCC.METHODS The present study employed the Web of Science Core Collection to identify all papers related to TAMs in HCC research.Utilizing the Analysis Platform of Bibliometrics,CiteSpace 6.2.R4,and Vosviewer 1.6.19,the study conducted a comprehensive analysis encompassing multiple dimensions such as publication quantity,countries of origin,affiliated institutions,publishing journals,contributing authors,co-references,author keywords,and emerging frontiers within this research domain.RESULTS A thorough examination was undertaken on 818 papers within this particular field,published between January 1,1985 to September 1,2023,which has witnessed a substantial surge in scholarly contributions since 2012,with a notable outbreak in 2019.China was serving as the central hub in this field,with Fudan University leading in terms of publications and citations.Chinese scholars have taken the forefront in driving the research expansion within this field.Hepatology emerged as the most influential journal in this field.The study by Qian and Pollard in 2010 received the highest number of co-citations.It was observed that the citation bursts of references coincided with the outbreak of publications.Notably,“tumor microenvironment”,“immunotherapy”,“prognostic”,“inflammation”,and“polarization”,etc.emerged as frequently occurring keywords in this field.Of particular interest,“immune evasion”,“immune infiltration”,and“cancer genome atlas”were identified as emerging frontiers in recent research.CONCLUSION The field of TAMs in HCC exhibited considerable potential,as evidenced by the promising prospects of immunotherapeutic interventions targeting TAMs for the amelioration of HCC.The emerging frontiers in this field primarily revolved around modulating the immunosuppressive characteristics of TAMs within a liver-specific immune environment,with a focus on how to counter immune evasion and reduce immune infiltration.展开更多
Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related mortality worldwide1.The primary treatment options for this disease are surgical resection and liver transplantation.Unfortunately,most HCC ca...Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related mortality worldwide1.The primary treatment options for this disease are surgical resection and liver transplantation.Unfortunately,most HCC cases are diagnosed in advanced stages and are inoperable.Even after surgery,the long-term prognosis remains unsatisfactory,because of a high recurrence rate.展开更多
Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and infl...Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.展开更多
Streptococcus suis serotype 2(SS2)is a zoonotic pathogen that can cause acute infection,such as septicemia in pigs and streptococcal toxic shock-like syndrome(STSLS)in humans,indicating that SS2 can evade innate immun...Streptococcus suis serotype 2(SS2)is a zoonotic pathogen that can cause acute infection,such as septicemia in pigs and streptococcal toxic shock-like syndrome(STSLS)in humans,indicating that SS2 can evade innate immunity.Macrophages perform essential antimicrobial functions in the innate immune system by engulfing and killing pathogens.Previously,a dna K mutant strain that showed impaired phagocytosis resistance ability was screened from the transposon mutant library of SS2,but the specific mechanism is unclear.In this study,we further demonstrated that DnaK was required for SS2 to be antiphagocytosed by macrophages and survive in adverse environments.A mouse challenge experiment indicated that DnaK promoted bacteremia and systemic dissemination of SS2,enhancing bacterial pathogenicity.Western blot and immunofluorescence results indicated that DnaK could be secreted by SS2 and was able to enter RAW264.7 macrophages.Then,the endocytic receptor LRP1 regulated by DnaK was identified through RNA sequencing(RNA-Seq).We found that DnaK decreased both the mRNA and protein levels of LRP1.Knockdown of the LRP1β-chain(LRP1β)significantly decreased the phagocytosis rate of the SS2 strain ZY05719,suggesting that LRP1 is a phagocytic receptor of SS2.Furthermore,inhibitor treatment assays revealed that DnaK decreased LRP1 protein levels through the transcription factor PPARγand the ubiquitin-proteasome system.In summary,DnaK contributes to the phagocytosis resistance of SS2 by decreasing LRP1 protein levels in macrophages,providing new insights into the antiphagocytosis mechanisms of SS2 and helping to understand its pathogenesis.展开更多
The NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain,leucine-rich repeats,and a pyrin domain.It i...The NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain,leucine-rich repeats,and a pyrin domain.It is a key regulator of inflammation in viral pneumonia(VP).Small-molecule inhibitors targeting various NLRP3 binding sites are advancing into early clinical trials,but their therapeutic utility is incompletely established.Xuanfei Baidu Formula(XF),clinically used for VP treatment,attenuates NLRP3 activation by hampering caspase-11 to impede polarization of pro-inflammatory macrophages in a model of lipopolysaccharide(LPS)-induced lung injury inmice.Herein,we demonstrate that XF attenuated influenza A virus(IAV)-induced lung inflammation as well as lung injury in immunocompetent(but not in macrophage-depleted)mice.RNA sequencing of sorted lung macrophages from IAV-infected mice revealed that XF inhibited activation of the NLRP3 inflammation and interleukin(IL)-1βproduction.Quantitative nuclear magnetic resonance of XF enabled us to develop XF-Comb1,a fixed-ratio combination of five bioactive compounds that recapitulated the bioactivity of XF in suppressing NLRP3 activation in macrophages in vitro and in vivo.Interestingly,XF-Comb1 inhibited assembly of the NLRP3 inflammasome through multi-site interactions with functional residues of NLRP3,apoptosis-associated speck-like protein containing caspase recruitment domain(ASC),and caspase-1.Taken together,this work advances the development of NLRP3 inhibitors by translating a complex herbal formula into defined bioactive compounds.展开更多
The molecular mechanisms by which the autonomic nervous system regulates immune cell function have become a popular research topic.The discovery that vagus nerve stimulation(VNS)alleviates endotoxemia has laid an impo...The molecular mechanisms by which the autonomic nervous system regulates immune cell function have become a popular research topic.The discovery that vagus nerve stimulation(VNS)alleviates endotoxemia has laid an important foundation for further study of the neuroimmune system.This review focuses on the latest insights related to intestinal neurons and macrophages(Mφs)and outlines the mechanisms underlying cholinergic control of inflammation and key electrophysiological VNS approaches for the treatment of inflammatory bowel disease(IBD).Mφs are the most important antigen-presenting cells in the human body and exist in various forms.In the gut,Mφs can maintain the intestinal balance by engulfing and digesting microorganisms.However,macrophage overactivation results in the production of excessive inflammatory mediators,which can damage the intestinal mucosa and induce an inflammatory response,leading to IBD.The role of cholinergic anti-inflammatory mechanisms in immune-mediated IBD have attracted substantial attention.Mφs are a special type of phagocytes that play a crucial role in maintaining intestinal homeostasis and movement.In the intestinal tract,Mφis classified into different subgroups based on its position in the parietal layer and is closely related to the microenvironment.展开更多
A recent study published in Science by Engleman et al.uncovered that erythropoietin(EPO)secreted by tumor cells can mediate the formation of a noninflamed immune microenvironment and promote tumor progression.1 Specif...A recent study published in Science by Engleman et al.uncovered that erythropoietin(EPO)secreted by tumor cells can mediate the formation of a noninflamed immune microenvironment and promote tumor progression.1 Specifically,in hepatocellular carcinoma(HCC),tumor cell-derived EPO binds to the erythropoietin receptor(EPOR)on tumor-associated macrophages(TAMs),thereby inhibiting the production of pro-inflammatory cytokines and reactive oxygen species(ROS)by Kupffer cells(KCs)and monocyte-derived macrophages(MDMs).This interaction facilitates the shift of macrophages from an inflamed to a noninflamed phenotype,ultimately promoting the progression of HCC.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most aggressive tumors worldwide.Chronic inflammation contributes to tumor evolution,and the infiltration of tumor-associated macrophages(TAMs),also known as M2-li...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most aggressive tumors worldwide.Chronic inflammation contributes to tumor evolution,and the infiltration of tumor-associated macrophages(TAMs),also known as M2-like macrophages,is associated with the most aggressive behavior.Therefore,these macrophages provide the primary growth and migratory factors to the tumor cells,including those of HCC.Current therapies are not well optimized for eliminating trans-formed cells or neutralizing the tumor immune microenvironment leukocytes,such as TAMs.Growth differentiation factor 11(GDF11)may represent a promi-sing dual therapeutic target due to its reported anti-tumorigenic and immuno-modulatory properties.AIM To characterize the effects of GDF11 in M2-like macrophages and the HCC cell interaction using a functional in vitro model.METHODS This research used THP-1 and Huh7 cell lines.We applied recombinant GDF11(50 ng/mL)every 24 hours on THP-1 differentiated macrophages with M2-like polarization using interleukin-4 and interleukin-13.Firstly,the GDF11 effects on signaling,viability,proliferation,metabolism,and redox state in macrophages were charac-terized.Subsequently,we extracted conditioned media(CM)from macrophages and performed indirect co-cultures with Huh7 cells.The functional parameters were proliferation and migration assays.Finally,we charac-terized secretion in the CM using the cytokine array membrane assay.RESULTS The present study demonstrated that GDF11 activates the canonical pathway Smad2/3 without cytotoxic or prolif-erative effects.We provide evidence that GDF11 also diminishes the pro-tumoral properties of M2-like macrophages.GDF11 promoted the reduction of the M2-like macrophage marker,cluster of differentiation 206,indicating a loss of pro-tumoral properties in these leukocytes.Furthermore,this molecule induced changes in metabolism and an increase in reactive oxygen species.Using CM derived from GDF11-treated M2-like macrophages,we observed a reduction in the proliferation and migratory capacity of liver cancer cells.Moreover,the cytokine profile was affected by GDF11 stimulus,demonstrating that this molecule alters the pro-tumoral properties of TAMs,which in turn impact the behavior of HCC-derived cells.CONCLUSION This in vitro study suggests that mitigating tumor-promoting or M2-like macrophages with GDF11 may be an effective strategy for controlling the aggressiveness of HCC.展开更多
Pyroptosis is a form of programmed cell death.Excessive or uncontrolled pyroptosis and the production of pro-inflammatory cytokines can lead to organ damage,circulatory failure,and even death.Gasdermin D(GSDMD)is the ...Pyroptosis is a form of programmed cell death.Excessive or uncontrolled pyroptosis and the production of pro-inflammatory cytokines can lead to organ damage,circulatory failure,and even death.Gasdermin D(GSDMD)is the primary executor of pyroptosis in macrophages.Upon cleavage,the N-terminal domain of GSDMD(GSDMD-N)is activated and oligomerizes to form pore-like structures in the plasma membrane,triggering pyroptosis and resulting in the release of pro-inflammatory cytokines such as interleukin-1β(IL-1β).As a key executioner molecule of pyroptosis,Gasdermin D plays a crucial role in pathogen-induced pyroptosis in macrophages.With in-depth research on the function and regulatory mechanisms of GSDMD,its role in pathogen-induced macrophage pyroptosis has gradually been revealed.This article elaborates on the mechanism of GSDMD in pathogen-induced macrophage pyroptosis,providing insights for exploring pyroptosis in the prevention and control of bacterial diseases,and identifying new therapeutic targets for bacterial infections.展开更多
Background:Microglia and brain macrophages contribute significantly to the tumor microenvironment in highly malignant glioblastoma where they are considered important drivers of tumor progression.A better understandin...Background:Microglia and brain macrophages contribute significantly to the tumor microenvironment in highly malignant glioblastoma where they are considered important drivers of tumor progression.A better understanding of the role of the brain macrophages present in glioblastoma appears crucial for improving therapeutic outcomes,especially in the context of novel immunotherapeutic approaches.Methods:We investigated the regulation of two well-established markers for microglia and brain macrophages,IBA1 and CD163,in relation to glioblastoma tumor necrosis using immunohistochemistry and modality fusion heatmaps of whole slide images obtained from adjacent tissue sections.Results:IBA1 and CD163 showed remarkable differences in relation to glioblastoma tumor necrosis.Generally,IBA1 immunoreactive cells were far less common in necrotic tissue areas than CD163-expressing cells.We also found extensive and frequently diffuse extracellular CD163 deposition,especially in hypocellular necrobiotic tumor regions where IBA1 was typically absent.Conclusions:Resident microglia seem more likely to be important for the diffuse infiltration of glioma cells in hypercellular tissue areas,whereas myeloid macrophages may be the main macrophage population in the wake of tumor necrosis.Since the necrotic niche with its interactions between microglia,brain macrophages,and glioblastoma/glioma stem cells is increasingly recognised as an important factor in tumor progression,further detailed studies of the macrophage populations in glioblastoma are warranted.展开更多
Objective miR-34c-3p is down-regulated in nasopharyngeal carcinoma(NPC).The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study.Methods Flow cytometry and imm...Objective miR-34c-3p is down-regulated in nasopharyngeal carcinoma(NPC).The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study.Methods Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86(CD86)and cluster of differentiation 206(CD206)expression;quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were employed to examine mRNA expression and protein levels;cell counting kit-8(CCK8)and transwell assays were employed to assess cell proliferation,migration,and invasion;and hematoxylin-eosin(HE)staining was employed to assess pathological changes in tumor tissues.Results Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11,and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation,migration,and invasion of NPC cells.The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues.Conclusion This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.展开更多
Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underp...Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.展开更多
Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic m...Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.展开更多
基金supported by Ministry of Science and Technology China Brain Initiative Grant,No.2022ZD0204702(to ZY)the National Natural Science Foundation of China,No.82371357(to LC)+2 种基金Foundation for Military Medicine,No.16QNP085(to ZY)Navy Medical University Basic Medical College“Yi Zhang”Basic Medical Talent Development and Support Program,Nos.JCYZRC-D-022(to TC)and JCYZRC-D-024(to HD)Science and Technology Innovation Special Fund of Shanghai Baoshan District,No.2023-E-05(to YW).
文摘Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
基金the support of the National Natural Science Foundation of China (Grant No.82272503)Natural Science Foundation of Zhejiang Province (Grant No. LQN25H060006)
文摘Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.
基金supported by grants from the Postdoctoral Science Foundation of China (Grant No. 2020M672072)。
文摘Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores the multifaceted roles of macrophage senescence in cancer, and establishes links between senescent macrophages and tumor progression from multiple perspectives, on the basis of the first comprehensive analysis of the molecular mechanisms and pathways involved. By systematically examining the diverse changes in senescent macrophages, this review integrates and analyzes their effects on tumors, thus offering a comprehensive and novel theoretical foundation, and practical insights for cancer treatment. Notably, by integrating current molecular research and therapeutic advancements, we summarize novel therapeutic strategies targeting senescent macrophages, including senolytics, senescence modulators, and cutting-edge immunotherapies, thereby highlighting the potential of senescent macrophages as a therapeutic target and introducing new opportunities for cancer treatment.
基金supported by the Beijing Natural Science Foundation (grant number: 7232060)National Key Research and Development Program of China (grant number: 2023YFC2307301)Top Level Public Health Technical Personnel Training Plan (grant number: LJRC-03-09)。
文摘Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.Results Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate(cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.Conclusions FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
基金supported by the Natural Science Foundation of Shandong Province,China(81072398).
文摘Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury.After injury,Schwann cells produce an inflammatory response and secrete various chemokines,inflammatory factors,and some other cytokines to promote the recruitment and M2 polarization of blood-derived macrophages,enhancing their phagocytotic ability,and thus play an important role in promoting nerve regeneration.Macrophages have also been found to promote vascular regeneration after injury,promote the migration and proliferation of Schwann cells along blood vessels,and facilitate myelination and axon regeneration.Therefore,there is a close interaction between Schwann cells and macrophages during peripheral nerve regeneration,but this has not been systematically summarized.In this review,the mechanisms of action of Schwann cells and macrophages in each other's migration and phenotypic transformation are reviewed from the perspective of each other,to provide directions for research on accelerating nerve injury repair.
基金Supported by the Sanming Project of Medicine in Shenzhen,No.SZZYSM202111002Shenzhen Medical Research Fund,No.B2302008+1 种基金Shenzhen Science and Technology Program,No.JCYJ20220531091809022,No.JSGG20210802093208023,No.JCYJ20220818103402006,and No.ZDSYS201606081515458Traditional Chinese Medicine Bureau of Guangdong Province,No.20231286.
文摘BACKGROUND Tumor-associated macrophages(TAMs)have demonstrated significant potential as a research and treatment approach for hepatocellular carcinoma(HCC).Nevertheless,a comprehensive quantitative analysis of TAMs in HCC remained insufficient.Therefore,the objective of this study was to employ bibliometric methods to investigate the development trends and research frontiers pertaining to this field.AIM To determine the knowledge structure and current research hotspots by bibliometric analysis of scholarly papers pertaining to TAMs in HCC.METHODS The present study employed the Web of Science Core Collection to identify all papers related to TAMs in HCC research.Utilizing the Analysis Platform of Bibliometrics,CiteSpace 6.2.R4,and Vosviewer 1.6.19,the study conducted a comprehensive analysis encompassing multiple dimensions such as publication quantity,countries of origin,affiliated institutions,publishing journals,contributing authors,co-references,author keywords,and emerging frontiers within this research domain.RESULTS A thorough examination was undertaken on 818 papers within this particular field,published between January 1,1985 to September 1,2023,which has witnessed a substantial surge in scholarly contributions since 2012,with a notable outbreak in 2019.China was serving as the central hub in this field,with Fudan University leading in terms of publications and citations.Chinese scholars have taken the forefront in driving the research expansion within this field.Hepatology emerged as the most influential journal in this field.The study by Qian and Pollard in 2010 received the highest number of co-citations.It was observed that the citation bursts of references coincided with the outbreak of publications.Notably,“tumor microenvironment”,“immunotherapy”,“prognostic”,“inflammation”,and“polarization”,etc.emerged as frequently occurring keywords in this field.Of particular interest,“immune evasion”,“immune infiltration”,and“cancer genome atlas”were identified as emerging frontiers in recent research.CONCLUSION The field of TAMs in HCC exhibited considerable potential,as evidenced by the promising prospects of immunotherapeutic interventions targeting TAMs for the amelioration of HCC.The emerging frontiers in this field primarily revolved around modulating the immunosuppressive characteristics of TAMs within a liver-specific immune environment,with a focus on how to counter immune evasion and reduce immune infiltration.
基金supported by the RGC Research Impact Fund(Grant No.R5008-22F).
文摘Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related mortality worldwide1.The primary treatment options for this disease are surgical resection and liver transplantation.Unfortunately,most HCC cases are diagnosed in advanced stages and are inoperable.Even after surgery,the long-term prognosis remains unsatisfactory,because of a high recurrence rate.
基金supported by grants from National Natural Science Foundation of China(32125038)National Key Research and Development Program of China(grant number 2023YFD1801100 and 2023YFD1800804)+1 种基金the Key Research and Development Program of the Xinjiang Uygur Autonomous Region(No.2024B02016)the 2115 Talent Development Program of China Agricultural University.
文摘Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.
基金funded by the National Key Research and Development Program of China(2021YFD1800400)the National Natural Science Foundation of China(32373018)+2 种基金Jiangsu Agriculture Science and Technology Innovation Fund,China(CX(23)1029)the Excellent Research Innovation Team in Universities in Anhui Province,China(2022AH010088)the Shennong Scholar Project of Anhui Agricultural University,China(rc392101)。
文摘Streptococcus suis serotype 2(SS2)is a zoonotic pathogen that can cause acute infection,such as septicemia in pigs and streptococcal toxic shock-like syndrome(STSLS)in humans,indicating that SS2 can evade innate immunity.Macrophages perform essential antimicrobial functions in the innate immune system by engulfing and killing pathogens.Previously,a dna K mutant strain that showed impaired phagocytosis resistance ability was screened from the transposon mutant library of SS2,but the specific mechanism is unclear.In this study,we further demonstrated that DnaK was required for SS2 to be antiphagocytosed by macrophages and survive in adverse environments.A mouse challenge experiment indicated that DnaK promoted bacteremia and systemic dissemination of SS2,enhancing bacterial pathogenicity.Western blot and immunofluorescence results indicated that DnaK could be secreted by SS2 and was able to enter RAW264.7 macrophages.Then,the endocytic receptor LRP1 regulated by DnaK was identified through RNA sequencing(RNA-Seq).We found that DnaK decreased both the mRNA and protein levels of LRP1.Knockdown of the LRP1β-chain(LRP1β)significantly decreased the phagocytosis rate of the SS2 strain ZY05719,suggesting that LRP1 is a phagocytic receptor of SS2.Furthermore,inhibitor treatment assays revealed that DnaK decreased LRP1 protein levels through the transcription factor PPARγand the ubiquitin-proteasome system.In summary,DnaK contributes to the phagocytosis resistance of SS2 by decreasing LRP1 protein levels in macrophages,providing new insights into the antiphagocytosis mechanisms of SS2 and helping to understand its pathogenesis.
基金supported by the National Natural Science Foundation of China(82141201,82405164,82204878,and 32170872)the Haihe Laboratory of Modern Chinese Medicine(Research and development of a universal treatment formula for respiratory viral infections)+3 种基金the National Key Research and Development Program of China(2021YFC1712905,2021YFC1712904,2020YFA0708004,2021YFE0200300,and 2023YFC2306202)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202002,ZYYCXTD-D-202001)the China Postdoctoral Science Foundation(2023M742626)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(CPSF)(GZC20231927).
文摘The NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain,leucine-rich repeats,and a pyrin domain.It is a key regulator of inflammation in viral pneumonia(VP).Small-molecule inhibitors targeting various NLRP3 binding sites are advancing into early clinical trials,but their therapeutic utility is incompletely established.Xuanfei Baidu Formula(XF),clinically used for VP treatment,attenuates NLRP3 activation by hampering caspase-11 to impede polarization of pro-inflammatory macrophages in a model of lipopolysaccharide(LPS)-induced lung injury inmice.Herein,we demonstrate that XF attenuated influenza A virus(IAV)-induced lung inflammation as well as lung injury in immunocompetent(but not in macrophage-depleted)mice.RNA sequencing of sorted lung macrophages from IAV-infected mice revealed that XF inhibited activation of the NLRP3 inflammation and interleukin(IL)-1βproduction.Quantitative nuclear magnetic resonance of XF enabled us to develop XF-Comb1,a fixed-ratio combination of five bioactive compounds that recapitulated the bioactivity of XF in suppressing NLRP3 activation in macrophages in vitro and in vivo.Interestingly,XF-Comb1 inhibited assembly of the NLRP3 inflammasome through multi-site interactions with functional residues of NLRP3,apoptosis-associated speck-like protein containing caspase recruitment domain(ASC),and caspase-1.Taken together,this work advances the development of NLRP3 inhibitors by translating a complex herbal formula into defined bioactive compounds.
基金Supported by the National Natural Science Foundation of China,No.82574996Xi’an Science and Technology Plan Project,No.23YXYJ0162+4 种基金Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZY-KJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.2025SF-YBXM-498The"Nursery Cultivation Plan"Project of Shaanxi Provincial Academy of Chinese Medicine and Shaanxi Provincial Hospital of Traditional Chinese Medicine for the Year 2025,No.2025-04the Fifth Batch of Outstanding Clinical Talents in Traditional Chinese Medicine Project of Shaanxi Province,Shaanxi Traditional Chinese Medicine Letter[2025],No.6.
文摘The molecular mechanisms by which the autonomic nervous system regulates immune cell function have become a popular research topic.The discovery that vagus nerve stimulation(VNS)alleviates endotoxemia has laid an important foundation for further study of the neuroimmune system.This review focuses on the latest insights related to intestinal neurons and macrophages(Mφs)and outlines the mechanisms underlying cholinergic control of inflammation and key electrophysiological VNS approaches for the treatment of inflammatory bowel disease(IBD).Mφs are the most important antigen-presenting cells in the human body and exist in various forms.In the gut,Mφs can maintain the intestinal balance by engulfing and digesting microorganisms.However,macrophage overactivation results in the production of excessive inflammatory mediators,which can damage the intestinal mucosa and induce an inflammatory response,leading to IBD.The role of cholinergic anti-inflammatory mechanisms in immune-mediated IBD have attracted substantial attention.Mφs are a special type of phagocytes that play a crucial role in maintaining intestinal homeostasis and movement.In the intestinal tract,Mφis classified into different subgroups based on its position in the parietal layer and is closely related to the microenvironment.
基金supported by the National Natural Science Foundation of China(32000799 to J.Zhang)Zhejiang Province Key Research and Development Program(2025C02058 to G.Ding)Zhejiang Association of Rehabilitation Medicine Foundation(ZKKY2024003 to G.Ding).
文摘A recent study published in Science by Engleman et al.uncovered that erythropoietin(EPO)secreted by tumor cells can mediate the formation of a noninflamed immune microenvironment and promote tumor progression.1 Specifically,in hepatocellular carcinoma(HCC),tumor cell-derived EPO binds to the erythropoietin receptor(EPOR)on tumor-associated macrophages(TAMs),thereby inhibiting the production of pro-inflammatory cytokines and reactive oxygen species(ROS)by Kupffer cells(KCs)and monocyte-derived macrophages(MDMs).This interaction facilitates the shift of macrophages from an inflamed to a noninflamed phenotype,ultimately promoting the progression of HCC.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most aggressive tumors worldwide.Chronic inflammation contributes to tumor evolution,and the infiltration of tumor-associated macrophages(TAMs),also known as M2-like macrophages,is associated with the most aggressive behavior.Therefore,these macrophages provide the primary growth and migratory factors to the tumor cells,including those of HCC.Current therapies are not well optimized for eliminating trans-formed cells or neutralizing the tumor immune microenvironment leukocytes,such as TAMs.Growth differentiation factor 11(GDF11)may represent a promi-sing dual therapeutic target due to its reported anti-tumorigenic and immuno-modulatory properties.AIM To characterize the effects of GDF11 in M2-like macrophages and the HCC cell interaction using a functional in vitro model.METHODS This research used THP-1 and Huh7 cell lines.We applied recombinant GDF11(50 ng/mL)every 24 hours on THP-1 differentiated macrophages with M2-like polarization using interleukin-4 and interleukin-13.Firstly,the GDF11 effects on signaling,viability,proliferation,metabolism,and redox state in macrophages were charac-terized.Subsequently,we extracted conditioned media(CM)from macrophages and performed indirect co-cultures with Huh7 cells.The functional parameters were proliferation and migration assays.Finally,we charac-terized secretion in the CM using the cytokine array membrane assay.RESULTS The present study demonstrated that GDF11 activates the canonical pathway Smad2/3 without cytotoxic or prolif-erative effects.We provide evidence that GDF11 also diminishes the pro-tumoral properties of M2-like macrophages.GDF11 promoted the reduction of the M2-like macrophage marker,cluster of differentiation 206,indicating a loss of pro-tumoral properties in these leukocytes.Furthermore,this molecule induced changes in metabolism and an increase in reactive oxygen species.Using CM derived from GDF11-treated M2-like macrophages,we observed a reduction in the proliferation and migratory capacity of liver cancer cells.Moreover,the cytokine profile was affected by GDF11 stimulus,demonstrating that this molecule alters the pro-tumoral properties of TAMs,which in turn impact the behavior of HCC-derived cells.CONCLUSION This in vitro study suggests that mitigating tumor-promoting or M2-like macrophages with GDF11 may be an effective strategy for controlling the aggressiveness of HCC.
基金Foshan High-Level Talent and Lingnan Scholar Research Initiation Project(Project No.:CGZ07001)Foshan Science and Technology Innovation Project(Project No.:2420001004253)Foshan Self-Funded Science and Technology Innovation Project(Project No.:2420001004253)。
文摘Pyroptosis is a form of programmed cell death.Excessive or uncontrolled pyroptosis and the production of pro-inflammatory cytokines can lead to organ damage,circulatory failure,and even death.Gasdermin D(GSDMD)is the primary executor of pyroptosis in macrophages.Upon cleavage,the N-terminal domain of GSDMD(GSDMD-N)is activated and oligomerizes to form pore-like structures in the plasma membrane,triggering pyroptosis and resulting in the release of pro-inflammatory cytokines such as interleukin-1β(IL-1β).As a key executioner molecule of pyroptosis,Gasdermin D plays a crucial role in pathogen-induced pyroptosis in macrophages.With in-depth research on the function and regulatory mechanisms of GSDMD,its role in pathogen-induced macrophage pyroptosis has gradually been revealed.This article elaborates on the mechanism of GSDMD in pathogen-induced macrophage pyroptosis,providing insights for exploring pyroptosis in the prevention and control of bacterial diseases,and identifying new therapeutic targets for bacterial infections.
基金funding but aspects of this work(computer analysis)were supported by an Australian Research Council(ARC)grant,DP150104472(MBG)The Australian Genomics and Outcomes of Glioma project was funded by a Cancer Council NSW Strategic Research Partnership Grant.
文摘Background:Microglia and brain macrophages contribute significantly to the tumor microenvironment in highly malignant glioblastoma where they are considered important drivers of tumor progression.A better understanding of the role of the brain macrophages present in glioblastoma appears crucial for improving therapeutic outcomes,especially in the context of novel immunotherapeutic approaches.Methods:We investigated the regulation of two well-established markers for microglia and brain macrophages,IBA1 and CD163,in relation to glioblastoma tumor necrosis using immunohistochemistry and modality fusion heatmaps of whole slide images obtained from adjacent tissue sections.Results:IBA1 and CD163 showed remarkable differences in relation to glioblastoma tumor necrosis.Generally,IBA1 immunoreactive cells were far less common in necrotic tissue areas than CD163-expressing cells.We also found extensive and frequently diffuse extracellular CD163 deposition,especially in hypocellular necrobiotic tumor regions where IBA1 was typically absent.Conclusions:Resident microglia seem more likely to be important for the diffuse infiltration of glioma cells in hypercellular tissue areas,whereas myeloid macrophages may be the main macrophage population in the wake of tumor necrosis.Since the necrotic niche with its interactions between microglia,brain macrophages,and glioblastoma/glioma stem cells is increasingly recognised as an important factor in tumor progression,further detailed studies of the macrophage populations in glioblastoma are warranted.
文摘Objective miR-34c-3p is down-regulated in nasopharyngeal carcinoma(NPC).The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study.Methods Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86(CD86)and cluster of differentiation 206(CD206)expression;quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were employed to examine mRNA expression and protein levels;cell counting kit-8(CCK8)and transwell assays were employed to assess cell proliferation,migration,and invasion;and hematoxylin-eosin(HE)staining was employed to assess pathological changes in tumor tissues.Results Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11,and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation,migration,and invasion of NPC cells.The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues.Conclusion This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.
文摘Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.
基金supported by the National Natural Science Foundation of China(No.82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)partially supported by Wuhan Kangchuang Biotechnology Co.,Ltd。
文摘Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.
