Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary d...Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.展开更多
The RING-type E3 ligase OsBBI1 regulates rice resistance against Magnaporthe oryzae through modifying cell wall defenses.In this study,we report the function of an OsBBI1 substrate,eukaryotic translation initiation fa...The RING-type E3 ligase OsBBI1 regulates rice resistance against Magnaporthe oryzae through modifying cell wall defenses.In this study,we report the function of an OsBBI1 substrate,eukaryotic translation initiation factor OseIF5A4,in rice immunity.OsBBI1 interacts with OseIF5A4 and other four members of the OseIF5A family.The RING domain in OsBBI1 and the eIF-5a domain in OseIF5A4 are critical for the OsBBI1-OseIF5A4 interaction.OsBBI1 ubiquitinates OseIF5A4 and mediates its degradation in vitro and in vivo.Moreover,the expression of OseIF5A4 was upregulated during early stage of compatible interaction but downregulated in incompatible interaction between rice and M.oryzae.Knockout of OseIF5A4 enhances rice immunity against M.oryzae and Xanthomonas oryzae pv.oryzae,boosts pattern-triggered immune responses,and strengthens pathogen-induced defense responses(e.g.,expression of defense genes,accumulation of reactive oxygen species and reinforcement of cell wall).However,overexpression of OseIF5A4 attenuates rice immunity and immune responses.These results demonstrate that OseIF5A4,a substrate of the immunity-associated E3 ligase OsBBI1,negatively regulates rice immunity against M.oryzae and X.oryzae pv.oryzae through modulating pathogen-induced defense responses,highlighting the importance of the protein translational machinery in rice immunity.展开更多
CD8^(+)T cell exhaustion,a critical challenge in the immune response to cancer,is characterized by a profound decline in the functionality of effector CD8^(+)T cells.This state of exhaustion is accompanied by the upre...CD8^(+)T cell exhaustion,a critical challenge in the immune response to cancer,is characterized by a profound decline in the functionality of effector CD8^(+)T cells.This state of exhaustion is accompanied by the upregulation of various inhibitory receptors and significant shifts in both transcriptional and epigenetic profiles,thus ultimately leading to inadequate tumor control.Therapeutic strategies aimed at reversing CD8^(+)T cell exhaustion have the potential to rejuvenate immune responses and enhance treatment efficacy.This review compiles current knowledge regarding the molecular mechanisms underlying CD8^(+)T cell exhaustion,including the roles of immune checkpoint molecules,the tumor microenvironment,metabolic reprogramming,transcription factors,and epigenetic modifications.Emerging therapeutic approaches designed to combat CD8^(+)T cell exhaustion are evaluated,with emphasis on the modulation of immune checkpoints;targeting of metabolic and transcriptional changes;and exploration of other innovative strategies,such as epigenetic editing and engineered CAR-T cells.Importantly,we expand the exhaustion concept to immune cells beyond CD8^(+)T cells,such as CD4^(+)T cells,natural killer cells,and myeloid populations,thereby highlighting the broader implications of systemic immunosuppression in the cancer context.Finally,we propose avenues for future research aimed at further elucidating the factors and molecular mechanisms associated with CD8^(+)T cell exhaustion,thereby underscoring the critical need for strategies aimed at reversing this state to improve outcomes in cancer immunotherapy.展开更多
In this editorial,we comment on the article by Xu et al published in the recent issue of the World Journal of Hepatology.The hepatitis B virus(HBV)has evolved sophisticated mechanisms to evade host innate immunity,a h...In this editorial,we comment on the article by Xu et al published in the recent issue of the World Journal of Hepatology.The hepatitis B virus(HBV)has evolved sophisticated mechanisms to evade host innate immunity,a hallmark of its persistent infections.This study highlights a pivotal role for HBV-encoded microRNA,specifically HBV-miR-3,in undermining the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)-IFN signaling axis.This pathway is critical for recognizing viral DNA and subsequent production of type I interferons,key antiviral cytokines.HBV-miR-3 achieves this immune evasion by directly downregulating the expression of cGAS,an essential DNA sensor,and STING,its downstream adaptor.By silencing these components,HBV-miR-3 disrupts the activation of downstream interferon regulatory factor 3 and Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells transcription factors,thereby blunting interferon beta production and antiviral gene expression.This strategy allows HBV to persist in hepatocytes by dampening innate immune responses and contributes to immune tolerance,fostering chronic infection.Understanding the role of HBV-miR-3 provides novel insights into HBV pathogenesis and identifies potential therapeutic targets to restore antiviral immunity.Targeting HBV-miR-3 or reactivating the cGAS-STING-IFN pathway could offer promising strategies to counteract HBV immune evasion and resolve chronic infection.展开更多
Cancer is a major threat to human health worldwide.Colorectal cancer(CRC),a highly prevalent malignant tumor,poses a significant public health challenge.Therefore,the identification of effective biomarkers is of great...Cancer is a major threat to human health worldwide.Colorectal cancer(CRC),a highly prevalent malignant tumor,poses a significant public health challenge.Therefore,the identification of effective biomarkers is of great significance[1].The NFKBIE gene encodes an inhibitor of nuclear factorκBε(IkBε).IκBε,a key regulator of the NF-κB signaling pathway,is closely associated with tumorigenesis.However,their roles in CRC remain unclear[2].Pan-cancer research is crucial for accelerating the identification of biomarkers and translational medical research,as it can reveal molecular commonalities and differences among different tumor types[3].展开更多
Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive imm...Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.展开更多
Objective:Lung cancer is the leading cause of cancer-related deaths worldwide.Chemotherapy is associated with side effects,such as damage to myeloid cells and a reduction in the number of immune cells in patients.In a...Objective:Lung cancer is the leading cause of cancer-related deaths worldwide.Chemotherapy is associated with side effects,such as damage to myeloid cells and a reduction in the number of immune cells in patients.In addition,tumor cells hijack the mitochondria of immune cells through tunnel nanotubes,thereby weakening immune ability.Methods:In this study the effects of direct mitochondria transplantation on cancer cell proliferation and chemotherapeutic sensitivity were determined,as well as anti-tumor immunity in in vitro and in vivo lung cancer models.Results:A combination of mitochondrial transplantation and cisplatin chemotherapy was shown for the first time to significantly improve immune infiltration of advanced non-small cell lung cancer(NSCLC)and overcome the shortcomings of cisplatin chemotherapy,including damage to myeloid cells and a reduction in the number of immune cells.Conclusions:The findings of the current study provide valuable recommendations for enhancing immune infiltration and augmenting anti-tumor efficacy during chemotherapy in advanced NSCLC.In addition,the findings support“mitochondrial transfer”as a novel paradigm in tumor treatment.展开更多
In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing i...In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.展开更多
Remodeling plant intracellular nucleotide-binding leucine-rich repeat immune receptors(NLRs)to engineer synthetic disease-resistance genes has emerged as a promising approach to achieving broad-spectrum disease resist...Remodeling plant intracellular nucleotide-binding leucine-rich repeat immune receptors(NLRs)to engineer synthetic disease-resistance genes has emerged as a promising approach to achieving broad-spectrum disease resistance.But strategies for expanding NLR recognition spectra[[1],[2],[3],[4],[5]]are often limited by the rapid evolution of pathogens and pests.In our recent study,we developed an innovative strategy to engineer broad-spectrum,durable and complete disease resistance in plants by remodeling autoactive NLRs into protease-activated switches[6].展开更多
Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept ...Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control.Investigations into trained immunity are rapidly advanc-ing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon.While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations,the prospects for its future application in clinical practice are promising.Here,we describe trained immunity as a biological process and explore the innate cues,epigenetic changes,and metabolic reprogram-ming activities that affect how trained immunity is induced.展开更多
Plants have evolved complex immune networks to adapt to survival needs,and their immune mechanisms have unique regulatory patterns to cope with different environments.In rice,the maintenance of immune balance involves...Plants have evolved complex immune networks to adapt to survival needs,and their immune mechanisms have unique regulatory patterns to cope with different environments.In rice,the maintenance of immune balance involves the synergistic action of many factors.Yue Wu et al.'s latest research results on the immunomodulatory mechanism of rice(ROD1 and the interaction between various proteins in rice)are introduced in this paper.展开更多
Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polariz...Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.展开更多
Wheat leaf rust,caused by Puccinia triticina(Pt),is one of the most devastating diseases in common wheat(Triticum aestivum L.)and can lead to heavy yield loss(Chai et al.2020).Leaf rust can result in 50%yield loss dur...Wheat leaf rust,caused by Puccinia triticina(Pt),is one of the most devastating diseases in common wheat(Triticum aestivum L.)and can lead to heavy yield loss(Chai et al.2020).Leaf rust can result in 50%yield loss during epidemic years(Huerta-Espino et al.2011;Gebrewahid et al.2020;Kolomiets et al.2021).Breeding varieties resistant to leaf rust have been recognized as the most effective and economical method to mitigate wheat losses caused by Pt.The narrow genetic basis of wheat constrains the number of cultivars resistant to leaf rust(Jin et al.2021).展开更多
In order to verify the synthesis pathway of linoleic acid(LA)to generate arachidonic acid(ARA),the functions ofΔ6 FAD and Elovl 5 in Apostichopus japonicus were tested by heterologous expression in Pichia pastoris.A ...In order to verify the synthesis pathway of linoleic acid(LA)to generate arachidonic acid(ARA),the functions ofΔ6 FAD and Elovl 5 in Apostichopus japonicus were tested by heterologous expression in Pichia pastoris.A 60-day feeding experiment was conducted to evaluate the effects of dietary LA and ARA on growth,polyunsaturated fatty acids(PUFA)biosynthesis and im-mune function of A.japonicus.Seven diets containing graded levels of LA or ARA were formulated,and one diet without PUFA was applied as a control.The results confirmed thatΔ6 FAD from A.japonicus has a double desaturation ability ofΔ6 andΔ5 for PUFA,and it works together with Elovl 5 enzyme play important roles in biosynthesis of ARA from LA.With increasing dietary LA from 4.9 to 12.1 g/kg,the expressions ofΔ6 FAD and Elovl 5,levels of LA,ARA and EPA in tissues increased,and the activities of ACP,AKP and CAT enzymes in intestine initially increased and then decreased.Additionally,by increasing dietary ARA from 0.7 to 3.8 g/kg,the contents of ALA,EPA and DHA decreased,while theΔ6 FAD expression and the activities of ACP,AKP and CAT in intes-tine increased significantly.Therefore,appropriate dietary levels of LA(12.1 g/kg)or ARA(3.8 g/kg)build a reasonable composi-tion of n-3/n-6 PUFA in A.japonicus,and improved its growth,antioxidant capacity and immunological defenses.展开更多
In a recent publication in Nature,Zhou and colleagues identified cyclic guanosine monophosphate(cGMP),a canonical phosphodiesterase 5(PDE5)substrate,as a key modulator of dendritic cell(DC)interstitial motility throug...In a recent publication in Nature,Zhou and colleagues identified cyclic guanosine monophosphate(cGMP),a canonical phosphodiesterase 5(PDE5)substrate,as a key modulator of dendritic cell(DC)interstitial motility through Rho kinase(ROCK)-dependent modulation of myosin-II activity.展开更多
Posttranslational modifications(PTMs)are essential regulatory mechanisms that play a critical role in plant immunity.Previously,we demonstrated that OsBBI1,a RING finger type E3 ligase,contributes to rice resistance a...Posttranslational modifications(PTMs)are essential regulatory mechanisms that play a critical role in plant immunity.Previously,we demonstrated that OsBBI1,a RING finger type E3 ligase,contributes to rice resistance against blast disease.In this study,we identified two Eps15 homology domain(EHD)-containing proteins,OsEHD1 and OsEHD2,as substrates of OsBBI1 and investigated their roles in rice immunity against Magnaporthe oryzae and Xanthomonas oryzae pv.oryzae(Xoo).We found that OsBBI1 ubiquitinated and promoted the degradation of OsEHD1 and OsEHD2 via ubiquitin/26S proteasome system(UPS)pathway.CRISPR/Cas9-mediated knockout of OsEHD1 and OsEHD2 led to enhanced immunity against M.oryzae and Xoo,improved expression of pathogen-induced immunity-associated genes,and strengthened pattern-triggered immunity(PTI),while overexpression of OsEHD1 resulted in opposite phenotypes.Additionally,OsEHD1 and OsEHD2 interacted with three SUMO proteins,OsSUMO3,OsSUMO5,or OsSUMO6,with SUMOylation sites in OsEHD1 and OsEHD2 being critical for these interactions.OsSUMO6 enhanced the stability of OsEHD1 and OsEHD2 to promote their negative immune regulation,whereas OsBBI1 reversed these negative immune functions.This study delineates a regulatory network of OsEHD1 and OsEHD2 proteins in rice immunity,highlighting the balance between OssBBI1-mediated ubiquitination and SUMOylation.展开更多
The aim of this study was to investigate the role of Dendrobium officinale crude polysaccharides(DOPS)and D.officinale purified polysaccharides(DOPS100)in attenuating immune dysfunction in subfertile mice.The results ...The aim of this study was to investigate the role of Dendrobium officinale crude polysaccharides(DOPS)and D.officinale purified polysaccharides(DOPS100)in attenuating immune dysfunction in subfertile mice.The results of the study revealed several noteworthy findings.First,DOPS and DOPS100 treatments led to significant improvement in weight gain and reversal of fatigue-related behaviors compared to the normal group.Second,both DOPS and DOPS100 showed effectiveness in reducing immune organ swelling,modulating immunoglobulin A(IgA)and immunoglobulin M(IgM)levels,and restoring complement(C3c and C4)levels.In addition,they demonstrated a significant ability to enhance the integrity of the intestinal mechanical barrier by differentially upregulating the tight junction proteins Occludin and Zonula occludens 1(ZO-1).In addition,it was found that DOPS100 specifically enhanced the CD4^(+)-T helper 17 cell(Th17)/regulatory T cell(Treg)immune axis in the gut,as evidenced by increased expression of forkhead box protein 3(Foxp3)as well as decreased expression of retinoic acid receptor-related orphan receptor γt(RORγt),and further modulation of interleukin 10(IL-10),interleukin 22(IL-22),and interleukin 17A(IL-17A)expression levels of inflammatory factors.These findings collectively suggest that DOPS100 holds significant potential in improving sub-healthy status by repairing the intestinal barrier,restoring local immune homeostasis,and activating the intestinal immune regulatory network.The study’s outcomes provide valuable insights into the therapeutic implications of DOPS and DOPS100 in addressing immune dysfunction in sub-healthy conditions.展开更多
Gibberella stalk rot(GSR)caused by Fusarium graminearum is one of the most devastating diseases of maize,seriously impacting maize yield and quality,as well as the ability to use technology of mechanical harvesting.En...Gibberella stalk rot(GSR)caused by Fusarium graminearum is one of the most devastating diseases of maize,seriously impacting maize yield and quality,as well as the ability to use technology of mechanical harvesting.Environmental conditions including photoperiod affect crop disease resistance.However,the mechanism underlying photoperiod-regulated maize GSR resistance remains unexplored.We found in this study that GSR resistance is regulated by the ZmPIF4.1(Phytochrome-Interacting Factor4)-ZmPTI1c(Pto-Interacting 1)-ZmMYB31 module coupled with photoperiod.The functional analysis of zmpti1c mutant indicated that ZmPTI1c negatively regulates maize GSR resistance.Short day promoted the disease progression in both zmpti1c and wild-type plants.ZmPTI1c promoter contains multiple predicted cis-acting elements for light responses.Yeast one-hybrid assay(Y1H),Electrophoretic mobility shift analysis(EMSA),and Dual-luciferase(LUC)reporter assays demonstrated that ZmPIF4.1 binds to the G-box in ZmPTI1c promoter and activates its expression.Moreover,expression levels of ZmPIF4 and ZmPTI1c were significantly higher under short day than under long day.ZmPTI1c interacted with and phosphorylated ZmMYB31.GSR resistance in zmmyb31 mutant was significantly increased than in wild type,indicating that ZmMYB31 also negatively regulated GSR resistance.Furthermore,ZmMYB31 suppressed the transcriptional activation of ZmPTI1c by ZmPIF4.1.Overall,ZmPIF4.1-ZmPTI1c-ZmMYB31negatively regulates maize immunity to GSR,which is likely modulated by photoperiod.展开更多
A recent publication by Espinosa-Carrasco et al.1has illuminated the critical roles of intratumoral immune triads-a unique cluster of CD4^(+)T cells,CD8^(+)T cells,and dendritic cells(DCs)-in mediating effective antit...A recent publication by Espinosa-Carrasco et al.1has illuminated the critical roles of intratumoral immune triads-a unique cluster of CD4^(+)T cells,CD8^(+)T cells,and dendritic cells(DCs)-in mediating effective antitumor responses.These triads ensure that CD8^(+)T cells receive the necessary help from CD4^(+)T cells,mediated via the same DC,to effectively targeting and destroying cancer cells.The article’s novel insight suggests a shift in focus from increasing the number of immune cells to optimizing their interactions within the tumor microenvironment.This groundbreaking study not only underscores the critical roles of CD4^(+)T cells and DCs,but also highlights the intricate interplay among immune cell subsets within the tumor microenvironment.展开更多
The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens...The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens.This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens,such as food antigens or pathogens.As an immune active organ,the liver functions as a gatekeeping barrier from the outside world,and it can create a rapid and strong immune response,under unfavorable conditions.However,the liver's assumed immune status is anti-inflammatory or immuno-tolerant.Dynamic interactions between the numerous populations of immune cells in the liver are key for maintaining the delicate balance between immune screening and immune tolerance.The anatomical structure of the liver can facilitate the preparation of lymphocytes,modulate the immune response against hepatotropic pathogens,and contribute to some of its unique immunological properties,particularly its capacity to induce antigen-specific tolerance.Since liver sinusoidal endothelial cell is fenestrated and lacks a basement membrane,circulating lymphocytes can closely contact with antigens,displayed by endothelial cells,Kupffer cells,and dendritic cells while passing through the sinusoids.Loss of immune tolerance,leading to an autoaggressive immune response in the liver,if not controlled,can lead to the induction of autoimmune or autoinflammatory diseases.This review mentions the unique features of liver immunity,and dysregulated immune responses in patients with autoimmune liver diseases who have a close association with inborn errors of immunity have also been the emphases.展开更多
文摘Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.
基金supported by grants from the National Natural Science Foundation of China(32072403 and 31871945)the National Key Research and Development Program of China(2016YFD0100600).
文摘The RING-type E3 ligase OsBBI1 regulates rice resistance against Magnaporthe oryzae through modifying cell wall defenses.In this study,we report the function of an OsBBI1 substrate,eukaryotic translation initiation factor OseIF5A4,in rice immunity.OsBBI1 interacts with OseIF5A4 and other four members of the OseIF5A family.The RING domain in OsBBI1 and the eIF-5a domain in OseIF5A4 are critical for the OsBBI1-OseIF5A4 interaction.OsBBI1 ubiquitinates OseIF5A4 and mediates its degradation in vitro and in vivo.Moreover,the expression of OseIF5A4 was upregulated during early stage of compatible interaction but downregulated in incompatible interaction between rice and M.oryzae.Knockout of OseIF5A4 enhances rice immunity against M.oryzae and Xanthomonas oryzae pv.oryzae,boosts pattern-triggered immune responses,and strengthens pathogen-induced defense responses(e.g.,expression of defense genes,accumulation of reactive oxygen species and reinforcement of cell wall).However,overexpression of OseIF5A4 attenuates rice immunity and immune responses.These results demonstrate that OseIF5A4,a substrate of the immunity-associated E3 ligase OsBBI1,negatively regulates rice immunity against M.oryzae and X.oryzae pv.oryzae through modulating pathogen-induced defense responses,highlighting the importance of the protein translational machinery in rice immunity.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82171810)the Program of Shandong Provincial Scientific and Technological Development of Traditional Chinese Medicine(Grant No.M-2023210)。
文摘CD8^(+)T cell exhaustion,a critical challenge in the immune response to cancer,is characterized by a profound decline in the functionality of effector CD8^(+)T cells.This state of exhaustion is accompanied by the upregulation of various inhibitory receptors and significant shifts in both transcriptional and epigenetic profiles,thus ultimately leading to inadequate tumor control.Therapeutic strategies aimed at reversing CD8^(+)T cell exhaustion have the potential to rejuvenate immune responses and enhance treatment efficacy.This review compiles current knowledge regarding the molecular mechanisms underlying CD8^(+)T cell exhaustion,including the roles of immune checkpoint molecules,the tumor microenvironment,metabolic reprogramming,transcription factors,and epigenetic modifications.Emerging therapeutic approaches designed to combat CD8^(+)T cell exhaustion are evaluated,with emphasis on the modulation of immune checkpoints;targeting of metabolic and transcriptional changes;and exploration of other innovative strategies,such as epigenetic editing and engineered CAR-T cells.Importantly,we expand the exhaustion concept to immune cells beyond CD8^(+)T cells,such as CD4^(+)T cells,natural killer cells,and myeloid populations,thereby highlighting the broader implications of systemic immunosuppression in the cancer context.Finally,we propose avenues for future research aimed at further elucidating the factors and molecular mechanisms associated with CD8^(+)T cell exhaustion,thereby underscoring the critical need for strategies aimed at reversing this state to improve outcomes in cancer immunotherapy.
文摘In this editorial,we comment on the article by Xu et al published in the recent issue of the World Journal of Hepatology.The hepatitis B virus(HBV)has evolved sophisticated mechanisms to evade host innate immunity,a hallmark of its persistent infections.This study highlights a pivotal role for HBV-encoded microRNA,specifically HBV-miR-3,in undermining the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)-IFN signaling axis.This pathway is critical for recognizing viral DNA and subsequent production of type I interferons,key antiviral cytokines.HBV-miR-3 achieves this immune evasion by directly downregulating the expression of cGAS,an essential DNA sensor,and STING,its downstream adaptor.By silencing these components,HBV-miR-3 disrupts the activation of downstream interferon regulatory factor 3 and Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells transcription factors,thereby blunting interferon beta production and antiviral gene expression.This strategy allows HBV to persist in hepatocytes by dampening innate immune responses and contributes to immune tolerance,fostering chronic infection.Understanding the role of HBV-miR-3 provides novel insights into HBV pathogenesis and identifies potential therapeutic targets to restore antiviral immunity.Targeting HBV-miR-3 or reactivating the cGAS-STING-IFN pathway could offer promising strategies to counteract HBV immune evasion and resolve chronic infection.
基金supported by the Basic Research and Talent Cultivation Program of Zhangjiakou City(No.2511028A).
文摘Cancer is a major threat to human health worldwide.Colorectal cancer(CRC),a highly prevalent malignant tumor,poses a significant public health challenge.Therefore,the identification of effective biomarkers is of great significance[1].The NFKBIE gene encodes an inhibitor of nuclear factorκBε(IkBε).IκBε,a key regulator of the NF-κB signaling pathway,is closely associated with tumorigenesis.However,their roles in CRC remain unclear[2].Pan-cancer research is crucial for accelerating the identification of biomarkers and translational medical research,as it can reveal molecular commonalities and differences among different tumor types[3].
基金Supported by Shenzhen Medical Research Fund,No.D2301010Shenzhen Science and Technology Program,No.RCYX20231211090346060。
文摘Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.
基金supported by the National Natural Science Foundation of China(Grant No.81922030)the International Cooperation Project of the Belt and Road(Grant No.20400750600)+1 种基金the Construction Project of Shanghai TCMintegrated Innovative Flagship Hospital[Grant No.ZY(2021-2023)-0205-05,ZXXT-202203]the Shanghai Municipal Commission of Health and Family Plan(Grant No.201840056).
文摘Objective:Lung cancer is the leading cause of cancer-related deaths worldwide.Chemotherapy is associated with side effects,such as damage to myeloid cells and a reduction in the number of immune cells in patients.In addition,tumor cells hijack the mitochondria of immune cells through tunnel nanotubes,thereby weakening immune ability.Methods:In this study the effects of direct mitochondria transplantation on cancer cell proliferation and chemotherapeutic sensitivity were determined,as well as anti-tumor immunity in in vitro and in vivo lung cancer models.Results:A combination of mitochondrial transplantation and cisplatin chemotherapy was shown for the first time to significantly improve immune infiltration of advanced non-small cell lung cancer(NSCLC)and overcome the shortcomings of cisplatin chemotherapy,including damage to myeloid cells and a reduction in the number of immune cells.Conclusions:The findings of the current study provide valuable recommendations for enhancing immune infiltration and augmenting anti-tumor efficacy during chemotherapy in advanced NSCLC.In addition,the findings support“mitochondrial transfer”as a novel paradigm in tumor treatment.
基金Supported by The Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘In this editorial,we comment on the article by Sá-Oliveira et al.We focus specifi-cally on the role of platelet-rich fibrin(PRF)in modulating innate immunity to enhance wound repair.The process of wound healing is complex and involves a coordinated series of biological events,including inflammation,cell proliferation,and tissue remodeling.The innate immune system is important in the early stages of wound repair,with inflammation being a crucial initial phase in tissue rege-neration.However,the inflammatory response should be regulated,as excessive or dysregulated inflammation can impair healing.Platelet concentrates,specifi-cally PRF,have originated as promising tools to optimize the tissue repair process.PRF is a second-generation platelet concentrate,and the release of growth factors(GFs)plays a determining role in several aspects of wound healing,including promoting cell proliferation,stimulating angiogenesis,and modulating inflam-mation.PRF forms a fibrin matrix that entraps platelets and GFs.This structure allows for their sustained release over time,which is believed to provide a more favorable microenvironment for tissue repair.Recent research by Sá-Oliveira et al has provided valuable evidence supporting the efficacy of PRF in promoting wound healing.Their study,conducted on an animal model,demonstrated that PRF-based dressings were more effective in accelerating wound closure in the early stages of the healing process,enhancing tissue repair,and modulating the inflammatory response.We explore how PRF's unique properties contribute to a more controlled and effective healing process.By examining these findings,we aim to highlight PRF's potential as a promising therapeutic strategy for improved wound management.
基金supported by the Biological Breeding-National Science and Technology Major Project(2024ZD04077).
文摘Remodeling plant intracellular nucleotide-binding leucine-rich repeat immune receptors(NLRs)to engineer synthetic disease-resistance genes has emerged as a promising approach to achieving broad-spectrum disease resistance.But strategies for expanding NLR recognition spectra[[1],[2],[3],[4],[5]]are often limited by the rapid evolution of pathogens and pests.In our recent study,we developed an innovative strategy to engineer broad-spectrum,durable and complete disease resistance in plants by remodeling autoactive NLRs into protease-activated switches[6].
文摘Trained immunity is a phenomenon in which brief exposure to an infectious agent or a vaccine can induce long-lasting changes in the host’s immune system,enhancing protection against subsequent infections.The concept of trained immunity has a significant impact on the field of immunology and has the potential to revolutionize how we approach vaccination and infectious disease control.Investigations into trained immunity are rapidly advanc-ing and have led to the development of new vaccines and immunotherapeutic strategies that harness the power of this phenomenon.While more investigations are needed to fully understand the mechanisms of trained immunity and its potential limitations,the prospects for its future application in clinical practice are promising.Here,we describe trained immunity as a biological process and explore the innate cues,epigenetic changes,and metabolic reprogram-ming activities that affect how trained immunity is induced.
基金support of the National Natural Science Foundation of China(32472594)the Independent Deployment Project of Institute of Zoology,Chinese Academy of Sciences(2023IOZ010).
文摘Plants have evolved complex immune networks to adapt to survival needs,and their immune mechanisms have unique regulatory patterns to cope with different environments.In rice,the maintenance of immune balance involves the synergistic action of many factors.Yue Wu et al.'s latest research results on the immunomodulatory mechanism of rice(ROD1 and the interaction between various proteins in rice)are introduced in this paper.
基金CAMs innovation Fund for Medical Sciences,Grant/Award Number:2022-12M-CoV19-005National Key Projects,Grant/Award Number:2023YFF0724900 and 2021YFF0702802。
文摘Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.
基金funded by the National Natural Science Foundation of China(32272083)。
文摘Wheat leaf rust,caused by Puccinia triticina(Pt),is one of the most devastating diseases in common wheat(Triticum aestivum L.)and can lead to heavy yield loss(Chai et al.2020).Leaf rust can result in 50%yield loss during epidemic years(Huerta-Espino et al.2011;Gebrewahid et al.2020;Kolomiets et al.2021).Breeding varieties resistant to leaf rust have been recognized as the most effective and economical method to mitigate wheat losses caused by Pt.The narrow genetic basis of wheat constrains the number of cultivars resistant to leaf rust(Jin et al.2021).
基金supported by the Natural Sci-ence Foundation of Shandong(Nos.ZR2022MC086 and ZR2023MC162).
文摘In order to verify the synthesis pathway of linoleic acid(LA)to generate arachidonic acid(ARA),the functions ofΔ6 FAD and Elovl 5 in Apostichopus japonicus were tested by heterologous expression in Pichia pastoris.A 60-day feeding experiment was conducted to evaluate the effects of dietary LA and ARA on growth,polyunsaturated fatty acids(PUFA)biosynthesis and im-mune function of A.japonicus.Seven diets containing graded levels of LA or ARA were formulated,and one diet without PUFA was applied as a control.The results confirmed thatΔ6 FAD from A.japonicus has a double desaturation ability ofΔ6 andΔ5 for PUFA,and it works together with Elovl 5 enzyme play important roles in biosynthesis of ARA from LA.With increasing dietary LA from 4.9 to 12.1 g/kg,the expressions ofΔ6 FAD and Elovl 5,levels of LA,ARA and EPA in tissues increased,and the activities of ACP,AKP and CAT enzymes in intestine initially increased and then decreased.Additionally,by increasing dietary ARA from 0.7 to 3.8 g/kg,the contents of ALA,EPA and DHA decreased,while theΔ6 FAD expression and the activities of ACP,AKP and CAT in intes-tine increased significantly.Therefore,appropriate dietary levels of LA(12.1 g/kg)or ARA(3.8 g/kg)build a reasonable composi-tion of n-3/n-6 PUFA in A.japonicus,and improved its growth,antioxidant capacity and immunological defenses.
基金supported by the National Natural Science Foundation of China(grant number:32000799)Key Research and Development Program of Zhejiang Province(grant number:2025C02058).
文摘In a recent publication in Nature,Zhou and colleagues identified cyclic guanosine monophosphate(cGMP),a canonical phosphodiesterase 5(PDE5)substrate,as a key modulator of dendritic cell(DC)interstitial motility through Rho kinase(ROCK)-dependent modulation of myosin-II activity.
基金supported by grants from the National Natural Science Foundation of China(32072403 and 31871945 to Fengming Song,and 32160455 to Yayun Yang)Postdoctoral Fellowship Program of CPSF(GZC20232353 to Yan Bi)the Opening Fund of Yunnan Provincial Key Laboratory of Agricultural Biotechnology to Yan Bi and Yayun Yang.
文摘Posttranslational modifications(PTMs)are essential regulatory mechanisms that play a critical role in plant immunity.Previously,we demonstrated that OsBBI1,a RING finger type E3 ligase,contributes to rice resistance against blast disease.In this study,we identified two Eps15 homology domain(EHD)-containing proteins,OsEHD1 and OsEHD2,as substrates of OsBBI1 and investigated their roles in rice immunity against Magnaporthe oryzae and Xanthomonas oryzae pv.oryzae(Xoo).We found that OsBBI1 ubiquitinated and promoted the degradation of OsEHD1 and OsEHD2 via ubiquitin/26S proteasome system(UPS)pathway.CRISPR/Cas9-mediated knockout of OsEHD1 and OsEHD2 led to enhanced immunity against M.oryzae and Xoo,improved expression of pathogen-induced immunity-associated genes,and strengthened pattern-triggered immunity(PTI),while overexpression of OsEHD1 resulted in opposite phenotypes.Additionally,OsEHD1 and OsEHD2 interacted with three SUMO proteins,OsSUMO3,OsSUMO5,or OsSUMO6,with SUMOylation sites in OsEHD1 and OsEHD2 being critical for these interactions.OsSUMO6 enhanced the stability of OsEHD1 and OsEHD2 to promote their negative immune regulation,whereas OsBBI1 reversed these negative immune functions.This study delineates a regulatory network of OsEHD1 and OsEHD2 proteins in rice immunity,highlighting the balance between OssBBI1-mediated ubiquitination and SUMOylation.
基金supported by the National Natural Science Foundation of China(82274134)the National Key R&D Plan(2017YFC1702200,2017YFC1702202)+1 种基金Key R&D Program Projects in Zhejiang Province(2020C04020)the Key Research and Development Program of Zhejiang Province(2025C02183).
文摘The aim of this study was to investigate the role of Dendrobium officinale crude polysaccharides(DOPS)and D.officinale purified polysaccharides(DOPS100)in attenuating immune dysfunction in subfertile mice.The results of the study revealed several noteworthy findings.First,DOPS and DOPS100 treatments led to significant improvement in weight gain and reversal of fatigue-related behaviors compared to the normal group.Second,both DOPS and DOPS100 showed effectiveness in reducing immune organ swelling,modulating immunoglobulin A(IgA)and immunoglobulin M(IgM)levels,and restoring complement(C3c and C4)levels.In addition,they demonstrated a significant ability to enhance the integrity of the intestinal mechanical barrier by differentially upregulating the tight junction proteins Occludin and Zonula occludens 1(ZO-1).In addition,it was found that DOPS100 specifically enhanced the CD4^(+)-T helper 17 cell(Th17)/regulatory T cell(Treg)immune axis in the gut,as evidenced by increased expression of forkhead box protein 3(Foxp3)as well as decreased expression of retinoic acid receptor-related orphan receptor γt(RORγt),and further modulation of interleukin 10(IL-10),interleukin 22(IL-22),and interleukin 17A(IL-17A)expression levels of inflammatory factors.These findings collectively suggest that DOPS100 holds significant potential in improving sub-healthy status by repairing the intestinal barrier,restoring local immune homeostasis,and activating the intestinal immune regulatory network.The study’s outcomes provide valuable insights into the therapeutic implications of DOPS and DOPS100 in addressing immune dysfunction in sub-healthy conditions.
基金supported financially by the grants from the JBGS[2021]002 project from the Jiangsu Governmentthe National Nature Science Foundation of China(32472095)+2 种基金the National Key Research and Development Program of China(2020YFE02029002)Collaborative Innovation Center for Modern Crop Production(CIC-MCP)to Xiquan Gaosupported in part by the high-performance computing platform of Bioinformatics Center,Nanjing Agricultural University。
文摘Gibberella stalk rot(GSR)caused by Fusarium graminearum is one of the most devastating diseases of maize,seriously impacting maize yield and quality,as well as the ability to use technology of mechanical harvesting.Environmental conditions including photoperiod affect crop disease resistance.However,the mechanism underlying photoperiod-regulated maize GSR resistance remains unexplored.We found in this study that GSR resistance is regulated by the ZmPIF4.1(Phytochrome-Interacting Factor4)-ZmPTI1c(Pto-Interacting 1)-ZmMYB31 module coupled with photoperiod.The functional analysis of zmpti1c mutant indicated that ZmPTI1c negatively regulates maize GSR resistance.Short day promoted the disease progression in both zmpti1c and wild-type plants.ZmPTI1c promoter contains multiple predicted cis-acting elements for light responses.Yeast one-hybrid assay(Y1H),Electrophoretic mobility shift analysis(EMSA),and Dual-luciferase(LUC)reporter assays demonstrated that ZmPIF4.1 binds to the G-box in ZmPTI1c promoter and activates its expression.Moreover,expression levels of ZmPIF4 and ZmPTI1c were significantly higher under short day than under long day.ZmPTI1c interacted with and phosphorylated ZmMYB31.GSR resistance in zmmyb31 mutant was significantly increased than in wild type,indicating that ZmMYB31 also negatively regulated GSR resistance.Furthermore,ZmMYB31 suppressed the transcriptional activation of ZmPTI1c by ZmPIF4.1.Overall,ZmPIF4.1-ZmPTI1c-ZmMYB31negatively regulates maize immunity to GSR,which is likely modulated by photoperiod.
文摘A recent publication by Espinosa-Carrasco et al.1has illuminated the critical roles of intratumoral immune triads-a unique cluster of CD4^(+)T cells,CD8^(+)T cells,and dendritic cells(DCs)-in mediating effective antitumor responses.These triads ensure that CD8^(+)T cells receive the necessary help from CD4^(+)T cells,mediated via the same DC,to effectively targeting and destroying cancer cells.The article’s novel insight suggests a shift in focus from increasing the number of immune cells to optimizing their interactions within the tumor microenvironment.This groundbreaking study not only underscores the critical roles of CD4^(+)T cells and DCs,but also highlights the intricate interplay among immune cell subsets within the tumor microenvironment.
文摘The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens.This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens,such as food antigens or pathogens.As an immune active organ,the liver functions as a gatekeeping barrier from the outside world,and it can create a rapid and strong immune response,under unfavorable conditions.However,the liver's assumed immune status is anti-inflammatory or immuno-tolerant.Dynamic interactions between the numerous populations of immune cells in the liver are key for maintaining the delicate balance between immune screening and immune tolerance.The anatomical structure of the liver can facilitate the preparation of lymphocytes,modulate the immune response against hepatotropic pathogens,and contribute to some of its unique immunological properties,particularly its capacity to induce antigen-specific tolerance.Since liver sinusoidal endothelial cell is fenestrated and lacks a basement membrane,circulating lymphocytes can closely contact with antigens,displayed by endothelial cells,Kupffer cells,and dendritic cells while passing through the sinusoids.Loss of immune tolerance,leading to an autoaggressive immune response in the liver,if not controlled,can lead to the induction of autoimmune or autoinflammatory diseases.This review mentions the unique features of liver immunity,and dysregulated immune responses in patients with autoimmune liver diseases who have a close association with inborn errors of immunity have also been the emphases.
