Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated ...Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated protein EspL,which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation.EspL knockout decreased Mtb intracellular survival,while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy.EspL interacts with ULK1 and promotes its phosphorylation at Ser^(757),leading to the inhibition of autophagy initiation.Additionally,overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo.Our findings revealed that EspL interferes with autophagy and antigen presenta-tion by suppressing ULK1 activation.These insights provide a novel understanding of Mtb pathogenicity.展开更多
Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of ...Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex （MHC） class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability ＇of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 （IL-10） and transforming growth factor beta （TGFβ） predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.展开更多
Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progres...Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progression of atherosclerosis mainly through interferon ct （IFN-ct） production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation ofpDCs in vitro in this study. Methods Peripheral blood mononuclear cells isolated by Ficoll cen- trifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with naive T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively. Results Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α （TNF-α） production from pDCs in a dose-dependent manner. In addition, the ability of priming na ve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment. Conclusion Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.展开更多
The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent stud...The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent studies suggested that RORγt+antigen-presenting cells(APCs),which encompass rare dendritic cell(DC)subsets and type 3 innate lymphoid cells(ILC3s),are key to pTreg induction.Here,we developed a mouse with reduced RORγt+APCs by deleting a specific cis-regulatory element of Rorc encoding RORγt.Single-cell RNA sequencing and flow cytometry analyses confirmed the depletion of a RORγt+DC subset and ILC3s.These mice showed a secondary reduction in pTregs,impaired tolerance to oral antigens,and an increase in T helper(Th)2 cells.Conversely,ILC3-deficient mice showed no pTregs or Th2 cell abnormalities.Lineage tracing revealed that RORγt+DCs share a lymphoid origin with ILC3s,consistent with their similar phenotypic traits.These findings highlight the role of lymphoid RORγt+DCs in maintaining intestinal immune balance and preventing conditions like food allergies.展开更多
Traditionally,macroautophagy(autophagy)is viewed as a pathway of cell survival.Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods o...Traditionally,macroautophagy(autophagy)is viewed as a pathway of cell survival.Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress.Interestingly,autophagy can also directly intersect with,and impact,other major pathways of cellular function.Here,we will review the contribution of autophagy to pathways of antigen presentation.The autophagy machinery acts to modulate both MHCⅠ and MHCⅡ antigen presentation.As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.展开更多
[Objective] This study aimed to investigate the changes of the transcriptional levels of molecules associated with endogenous antigen processing and presenta- tion in porcine skin-derived dendritic cells infected with...[Objective] This study aimed to investigate the changes of the transcriptional levels of molecules associated with endogenous antigen processing and presenta- tion in porcine skin-derived dendritic cells infected with PCV2 in vivo. [Method] Healthy 40-day-old Landrace piglets were infected with porcine circovirus type 2 （PCV2） and euthanized on the 34, 7rd, 14th, 21st and 35th d post inoculation （DPI）. The porcine skin-derived dendritic cells （DCs） were collected to analyze the transcrip- tional levels of molecules （LMP7, UBP, MHC-I, calreticulin） associated with endogenous antigen processing and presentation by using real-time fluorescent quantitative PCR （real-time FQ-PCR）. [Result] The results showed that the level of LMP7 mR- NAs was reduced significantly on the 3DPI （P〈0.05）; the level of UBP mRNAs was consistently up-regulated, which increased significantly on the 21DPI and 35DPI （P〈 0.05）; the level of MHC-I mRNAs was significantly down-regulated on the 7DPI （P〈 0.05）; the level of calreticulin mRNAs was up-regulated slightly without significant dif- ference. [Conclusion] PCV2 can inhibit the endogenous antigen processing and presentation ability of porcine skin-derived DCs at early stages of infection.展开更多
Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response.Non-self intracellular proteins are processed into short peptides and...Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response.Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class I molecules assisted by several chaperone proteins to form trimeric complex.MHC class I complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells.The cells presenting non-self peptides are cleared by CD8 positive T cells.In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class I expression must be carefully regulated.Many of the cellular components involved in antigen processing and class I presentation are known and their various functions are now becoming clearer.Cellular & Molecular Immunology.2004;1(1):22-30.展开更多
The liver is an important immunological organ that controls systemic tolerance.The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance.Orches...The liver is an important immunological organ that controls systemic tolerance.The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance.Orchestrating the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment,which Is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating leukocytes.In response to pathogens or autoantigens,tolerance is disrupted by unknown mechanisms.Intrahepatic parenchymal and nonparenchymal cells exhibit unique antigen-presenting properties.The presentation of microbial and endogenous lipid-,metabolite-and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or tolerance.Perturbation of this balance results in autoimmune liver diseases,such as autoimmune hepatitis,primary biliary cholangitis,and primary sclerosing cholangitis.Although the exact etiologies of these autoimmune liver diseases are unknown,it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids,as well as alterations in bile acid composition,may result in changes in effector cell activation and polarization and may reduce or impair protective antiinflammatory regulatory T and B cell responses.Additionally,the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different(non)immune cells in the liver may play a role in the induction of hepatic inflammation and tolerance.Here,we summarize emerging aspects of antigen presentation,autoantibody production,and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.展开更多
Immunization has long played essential roles in preventing diseases.However,the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet.Here,we describe the use of acupoint de...Immunization has long played essential roles in preventing diseases.However,the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet.Here,we describe the use of acupoint delivery of nanovaccines(ADN)to elicit dual-niche immunological priming.ADN can simultaneously stimulate mast cell-assisted maturation of dendritic cells at the acupoint and enable direct delivery of nanovaccines into the draining lymph nodes.We demonstrate that ADN not only provokes antigen presentation by lymph node-resident CD8α^(+)dendritic cells,but also induces the accumulation of nanovaccines in B-cell zones,amplifying antigen-specific cytotoxic T lymphocyte responses and immunoglobulin G antibody expression in draining lymph nodes.ADN also generates systemic immune responses by causing immune memory and preventing T-cell anergy in the spleen.Further supported by evoking effective antitumor responses and high-level antiviral antibodies in mice,ADN provides a simple yet versatile platform for advanced nanovaccination.展开更多
An immunostimulatory factor was identified to be secreted by antigen-pulsed maorophages. This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo. Further in v...An immunostimulatory factor was identified to be secreted by antigen-pulsed maorophages. This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo. Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a genetically-restricted antigen specific factor (ASF). The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-pulsed maorophages with T lymphocytes, and then spleen cells, and finally the TNP-coated sheep red blood cells.展开更多
The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota. Inflammatory bowel disease (IBD) involves a breakdown in tolerance...The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota. Inflammatory bowel disease (IBD) involves a breakdown in tolerance towards the microbiota. Dendritic cells (DC), macrophages (MΦ) and B-cells are known as professional antigen-presenting cells (APC) due to their specialization in presenting processed antigen to T-cells, and in turn shaping types of T-cell responses generated. Intestinal DC are migratory cells, unique in their ability to generate primary T-cell responses in mesenteric lymph nodes or Peyer’s patches, whilst MΦ and B-cells contribute to polarization and differentiation of secondary T-cell responses in the gut lamina propria. The antigen-sampling function of gut DC and MΦ enables them to sample bacterial antigens from the gut lumen to determine types of T-cell responses generated. The primary function of intestinal B-cells involves their secretion of large amounts of immunoglobulin A, which in turn contributes to epithelial barrier function and limits immune responses towards to microbiota. Here, we review the role of all three types of APC in intestinal immunity, both in the steady state and in inflammation, and how these cells interact with one another, as well as with the intestinal microenvironment, to shape mucosal immune responses. We describe mechanisms of maintaining intestinal immune tolerance in the steady state but also inappropriate responses of APC to components of the gut microbiota that contribute to pathology in IBD.展开更多
AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cel...AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cell line(Raw 264.7),mouse primary antigen-presenting cells(APCs,MHCII+) and CD11c+dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively.To confirm the anti-inflammatory effects of cinnamon extract in vivo,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression prof iles in inflamed tissue.RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells(DCs) by suppressing expression of co-stimulatory molecules(B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase(COX)-2.Cinnamon extract induced regulatory DCs(rDCs) that produce low levels of pro-inflammatory cytokines [interleukin(IL)-1β,IL-6,IL-12,interferon(IFN)-γ and tumor necrosis factor(TNF)-α] while expressing high levels of immunoregulatory cytokines(IL-10 and transforming growth factor-β).In addition,rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines(IL-1β,IFN-γ and TNF-α),while enhancing IL-10 levels.CONCLUSION:Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10+ regulatory T cells.展开更多
Systemic lupus erythematosus （SLE） is a typical autoimmune disease involving multiple systems and organs. Ample evidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune d...Systemic lupus erythematosus （SLE） is a typical autoimmune disease involving multiple systems and organs. Ample evidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This study was undertaken to investigate the mechanisms of interaction between antigen presenting cells （APCs） and an autoreactive T cell （ATLI） clone obtained from lupus-prone BXSB mice. ATLI cells, either before or after 7-ray irradiation, were able to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able to stimulate the proliferation of resting ATL 1 cells at a responder/stimulator （R/S） ratio of 1/2.5. Dendritic cells （DCs） were much more powerful stimulators for ATLI cells on a per cell basis. The T cell stimulating ability ofmacrophages and B cells, but not DCs, was sensitive to T-ray irradiation. Monoclonal antibodies against mouse MHC-Ⅱ and CD4 were able to block DC-mediated stimulation of ATL 1 proliferation, indicating cognate recognition between ATL 1 and APCs. Our data suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotal role in keeping the momentum of autoimmune responses leading to autoimmune diseases.展开更多
Nanoparticles represent a heterogeneous collection of materials,whether natural or synthetic,with dimensions aligning in the nanoscale.Because of their intense manifestation with the immune system,they can be harveste...Nanoparticles represent a heterogeneous collection of materials,whether natural or synthetic,with dimensions aligning in the nanoscale.Because of their intense manifestation with the immune system,they can be harvested for numerous bio-medical and biotechnological advancements mainly in cancer treatment.This review article aims to scrutinize various types of nanoparticles that interact differently with immune cells like macrophages,dendritic cells,T lymphocytes,and natural killer(NK)cells.It also underscores the importance of knowing how nanoparticles influence immune cell functions,such as the production of cytokines and the presentation of antigens which are crucial for effective cancer immunotherapy.Hence overviews of bio-molecular mechanisms are provided.Nanoparticles can improve antigen presentation,boost T-cell responses,and overcome the immunosuppressive tumor environment.The regulatory mechanisms,signaling pathways,and nanoparticle characteristics are also presented for a comprehensive understanding.We review the nanotechnology platform options and challenges in nanoparticlesbased immunotherapy,from an immunotherapy perspective including precise targeting,immune modulation,and potential toxicity,as well as personalized approaches based on individual patient and tumor characteristics.The development of emerging multifunctional nanoparticles and theranostic nanoparticles will provide new solutions for the precision and efficiency of cancer therapies in next-generation practice.展开更多
The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive c...The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive carrier state,chronic hepatitis,cirrhosis,hepatocellular carcinoma,to liver failure,depending on the success or failure of immune response to HBV.Genome-wide association studies(GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits.In this review,we discuss GWAS for persistence of HBV infection,antibody response to hepatitis B vaccine,and HBV-related advanced liver diseases.HBV persistence is associated with multiple genes with diverse roles in immune mechanisms.The strongest associations are found within the classical human leukocyte antigen(HLA) genes,highlighting the central role of antigen presentation in the immune response to HBV.Associated variants affect both epitope binding specificities and expression levels of HLA molecules.Several other susceptibility genes regulate the magnitude of adaptive immune responses,determining immunity vs tolerance.HBV persistence and nonresponse to vaccine share the same risk variants,implying overlapping genetic bases.On the other hand,the risk variants for HBV-related advanced liver diseases are largely different,suggesting different host-virus dynamics in acute vs chronic HBV infections.The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.展开更多
The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurre...The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurrence and development of Parkinson’s disease.However,it remains unclear whether oxidative stress induces Parkinson’s disease through the MHC-I pathway.In the present study,polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium(MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease mouse model.The findings revealed that MHC-I was expressed in both models.To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells,immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8(CD8)+T cell infiltration in the substantia nigra of MPTP-treated mice.The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+T cells.Moreover,in MPTP-induced Parkinson’s disease model mice,the genetic knockdown of endogenous MHC-I,which was caused by injecting specific adenovirus into the substantia nigra,led to a significant reduction in CD8+T cell infiltration and alleviated dopaminergic neuronal death.To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation,the expression of PTEN-induced kinase 1(PINK1)was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA(siRNA),and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells.Taken together,MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation,thus rendering dopaminergic neurons susceptible to immune cells and degeneration.This may be one of the mechanisms of oxidative stress-induced Parkinson’s disease,and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation.All animal experiments were approved by the Southern Medical University Ethics Committee(No.81802040,approved on February 25,2018).展开更多
The role of the p38 signaling pathway in the innate and adaptive immune responses has been well documented,especially in inflammatory cytokine production by dendritic cells(DCs).However,whether the p38 signaling pathw...The role of the p38 signaling pathway in the innate and adaptive immune responses has been well documented,especially in inflammatory cytokine production by dendritic cells(DCs).However,whether the p38 signaling pathway affects the important antigen(Ag)presentation function of DCs remains largely unknown.In this study,we reported that the deletion of p38αresulted in an impaired cross-presentation ability of CD8^(+) conventional DCs(cDCs)and a reduction in the direct presentation ability of CD8−cDCs ex vivo.Further study revealed that p38αhad a crucial role in Ag processing by CD8^(+) cDCs but did not affect the Ag uptake or co-stimulation of T cells.Moreover,p38αdeficiency led to reduced cross-priming of T cells in vivo.The production of the IL-12p40 and IL-12p70 cytokines by p38α-deficient cDCs was also significantly reduced.Our study identified a new role for p38αin modulating the important antigen cross-presentation function of DCs.展开更多
Activating humoral and cellular immunity in lymph nodes(LNs)of nanoparticle-based vaccines is critical to controlling tumors.However,how the physical properties of nanovaccine carriers orchestrate antigen capture,lymp...Activating humoral and cellular immunity in lymph nodes(LNs)of nanoparticle-based vaccines is critical to controlling tumors.However,how the physical properties of nanovaccine carriers orchestrate antigen capture,lymphatic delivery,antigen presentation and immune response in LNs is largely unclear.Here,we manufactured gold nanoparticles(AuNPs)with the same size but different shapes(cages,rods,and stars),and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas.Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes.On lymphatic delivery,both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention.A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity,which is mediated by CD4^(+)T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study.Interestingly,cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8^(+)T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study.These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs,and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.展开更多
Objective: To study the effects of hyperbaric air exposure on the functions of peritoneal macrophages of mice. Methods: Forty-eight mice were equally randomized to 6 groups: (1) normal air group (NA); (2) hyperbaric a...Objective: To study the effects of hyperbaric air exposure on the functions of peritoneal macrophages of mice. Methods: Forty-eight mice were equally randomized to 6 groups: (1) normal air group (NA); (2) hyperbaric air group 1 (HA1); (3) hyperbaric air group 2 (HA2); (4) hyperbaric air group 3 (HA3); (5) hyperbaric oxygen group (HO);(6) hyperbaric nitrogen group (HN). Every group was exposed to corresponding pressure for 60 min, twice a day for 3 d. Peritoneal macrophages were obtained at the corresponding time to observe the changes of phagocytosis, acid phos-phatase, antigen presentation function and the produce of NO and TNF-α. Results: Compared with those in NA group, the activity of phagocytosis, acid phosphatase, antigen presentation function and the produce of NO and TNF-a were markedly inhibited in hyperbaric oxygen group and hyperbaric air group 1 ( P < 0.05, P < 0.01) and they changed little in HN group. These changes could disappear in 3 - 5 d. Conclusion: The functions of mice peritoneal macrophages were obviously inhibited in simulated air diving environment and hyperoxia may play an important role in it.展开更多
Background and Objectives Autoimmune reaction may play an important role in the pathogenesis and progress in virus myocarditis. Dendritic cells are the initiators of immune reaction to foreign antigens and are conside...Background and Objectives Autoimmune reaction may play an important role in the pathogenesis and progress in virus myocarditis. Dendritic cells are the initiators of immune reaction to foreign antigens and are considered to be key players in the induction and maintenance of autoimmune reactions. This study was undertaken to investigate the role of DC in mice with virus myocarditis. Methods and Results Fifty Balb/c mice were injected Coxsackie B3 virus to induce myocarditis and ten mice were injected culture liquid as control group. The hearts of virus - infected mice were harvested on day 3, 7, 14, 28 after the injection. All the hearts were sliced to do HE staining, MHC Ⅱ antigen and S - 100 protein immunohistochemical staining. The inflammation response and expression of MHC Ⅱ antigen and S - 100 protein positive stained cells were observed. The MHC Ⅱ antigen positive score were 1.42±0.95, 2.24 ±1. 00, 3. 23± 1. 16, 2. 58 ± 1. 05 respectively in group 3d, 7 d, 14 d, 28 d, which were significant different from control group(0. 50 ±0.75, P <0. 05). The S-100 positive staining cells in control group was 3. 2±1. 0. And the numbers were 6. 7 ± 1. 4 , 16. 4 ± 2. 5 , 21. 2±3. 3 , 13. 4 ± 2. 3 respectively in group 3 d, 7 d, 14 d, 28 d, and there were significant differences compared with the control group ( P < 0. 01) . Conclusions Immune reaction was involved in the pathogenesis in Coxsackie B3 virus - induced myocarditis in mouse, and dendritic cell might play an important role in the immune reaction.展开更多
基金supported by the National Natural Science Foundation of China under grant number U21A20259the National Key Research and Development Program of China under grant number 2021YFD1800401.
文摘Mycobacterium tuberculosis(Mtb)employs multiple mechanisms,such as phagocytosis and autophagy,to evade innate immune clearance and establish infection.In the present study,we identified the ESX-1 secretion-associated protein EspL,which promotes Mtb survival by inhibiting phagosome maturation and autophagy initiation.EspL knockout decreased Mtb intracellular survival,while EspL overexpression increased bacterial survival by interfering with phagocytosis and autophagy.EspL interacts with ULK1 and promotes its phosphorylation at Ser^(757),leading to the inhibition of autophagy initiation.Additionally,overexpression of EspL reduced antigen presentation and T-cell responses both in vitro and in vivo.Our findings revealed that EspL interferes with autophagy and antigen presenta-tion by suppressing ULK1 activation.These insights provide a novel understanding of Mtb pathogenicity.
基金Supported by Development funds from Section of Gastroenterology/Hepatology, Internal Medicine, University of Nebraska Medical Center
文摘Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex （MHC） class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability ＇of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 （IL-10） and transforming growth factor beta （TGFβ） predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.
文摘Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progression of atherosclerosis mainly through interferon ct （IFN-ct） production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation ofpDCs in vitro in this study. Methods Peripheral blood mononuclear cells isolated by Ficoll cen- trifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with naive T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively. Results Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α （TNF-α） production from pDCs in a dose-dependent manner. In addition, the ability of priming na ve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment. Conclusion Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.
文摘The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent studies suggested that RORγt+antigen-presenting cells(APCs),which encompass rare dendritic cell(DC)subsets and type 3 innate lymphoid cells(ILC3s),are key to pTreg induction.Here,we developed a mouse with reduced RORγt+APCs by deleting a specific cis-regulatory element of Rorc encoding RORγt.Single-cell RNA sequencing and flow cytometry analyses confirmed the depletion of a RORγt+DC subset and ILC3s.These mice showed a secondary reduction in pTregs,impaired tolerance to oral antigens,and an increase in T helper(Th)2 cells.Conversely,ILC3-deficient mice showed no pTregs or Th2 cell abnormalities.Lineage tracing revealed that RORγt+DCs share a lymphoid origin with ILC3s,consistent with their similar phenotypic traits.These findings highlight the role of lymphoid RORγt+DCs in maintaining intestinal immune balance and preventing conditions like food allergies.
基金supported by a National Health and Medical Research Council of Australia Career Development Award.
文摘Traditionally,macroautophagy(autophagy)is viewed as a pathway of cell survival.Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress.Interestingly,autophagy can also directly intersect with,and impact,other major pathways of cellular function.Here,we will review the contribution of autophagy to pathways of antigen presentation.The autophagy machinery acts to modulate both MHCⅠ and MHCⅡ antigen presentation.As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.
基金Supported by Natural Science Foundation of Beijing "Effect of porcine skin-derived dendritic cells on PCV infection" (6062006)Beijing Organization Department Project"Influence of PCV infection on bone marrow cell differentiation" (20061D0502100282)~~
文摘[Objective] This study aimed to investigate the changes of the transcriptional levels of molecules associated with endogenous antigen processing and presenta- tion in porcine skin-derived dendritic cells infected with PCV2 in vivo. [Method] Healthy 40-day-old Landrace piglets were infected with porcine circovirus type 2 （PCV2） and euthanized on the 34, 7rd, 14th, 21st and 35th d post inoculation （DPI）. The porcine skin-derived dendritic cells （DCs） were collected to analyze the transcrip- tional levels of molecules （LMP7, UBP, MHC-I, calreticulin） associated with endogenous antigen processing and presentation by using real-time fluorescent quantitative PCR （real-time FQ-PCR）. [Result] The results showed that the level of LMP7 mR- NAs was reduced significantly on the 3DPI （P〈0.05）; the level of UBP mRNAs was consistently up-regulated, which increased significantly on the 21DPI and 35DPI （P〈 0.05）; the level of MHC-I mRNAs was significantly down-regulated on the 7DPI （P〈 0.05）; the level of calreticulin mRNAs was up-regulated slightly without significant dif- ference. [Conclusion] PCV2 can inhibit the endogenous antigen processing and presentation ability of porcine skin-derived DCs at early stages of infection.
文摘Presentation of antigenic peptide to T cells by major histocompatibility complex (MHC) class I molecules is the key to the cellular immune response.Non-self intracellular proteins are processed into short peptides and transported into endoplasmic reticulum (ER) where they are assembled with class I molecules assisted by several chaperone proteins to form trimeric complex.MHC class I complex loaded with optimised peptides travels to the cell surface of antigen presentation cells to be recognised by T cells.The cells presenting non-self peptides are cleared by CD8 positive T cells.In order to ensure that T cells detect an infection or mutation within the target cells the process of peptide loading and class I expression must be carefully regulated.Many of the cellular components involved in antigen processing and class I presentation are known and their various functions are now becoming clearer.Cellular & Molecular Immunology.2004;1(1):22-30.
基金supported by funding from the German Research Foundation(DFG),Collaborative Research grants within the CRC841(SFB841:"Liver inflammation:Infection,immune regulation und consequences"),projects B01 to A.K.H.and G.T.,B09 to L.D.the Clinical Research Group KF0306("Primary Sclerosing Cholangitis"),project 04 to G.T.
文摘The liver is an important immunological organ that controls systemic tolerance.The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance.Orchestrating the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment,which Is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating leukocytes.In response to pathogens or autoantigens,tolerance is disrupted by unknown mechanisms.Intrahepatic parenchymal and nonparenchymal cells exhibit unique antigen-presenting properties.The presentation of microbial and endogenous lipid-,metabolite-and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or tolerance.Perturbation of this balance results in autoimmune liver diseases,such as autoimmune hepatitis,primary biliary cholangitis,and primary sclerosing cholangitis.Although the exact etiologies of these autoimmune liver diseases are unknown,it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids,as well as alterations in bile acid composition,may result in changes in effector cell activation and polarization and may reduce or impair protective antiinflammatory regulatory T and B cell responses.Additionally,the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different(non)immune cells in the liver may play a role in the induction of hepatic inflammation and tolerance.Here,we summarize emerging aspects of antigen presentation,autoantibody production,and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.
基金supported by the National Key Research and Development Program of China(2021YFA0909400)the National Natural Science Foundation of China(22425505,32301099,and 21834007)+2 种基金the Shanghai Sailing Program(22YF1424200)the Interdisciplinary Program of Shanghai Jiao Tong University(YG2022QN032)the Xiangfu Lab Research Project(XF012022E0100).
文摘Immunization has long played essential roles in preventing diseases.However,the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet.Here,we describe the use of acupoint delivery of nanovaccines(ADN)to elicit dual-niche immunological priming.ADN can simultaneously stimulate mast cell-assisted maturation of dendritic cells at the acupoint and enable direct delivery of nanovaccines into the draining lymph nodes.We demonstrate that ADN not only provokes antigen presentation by lymph node-resident CD8α^(+)dendritic cells,but also induces the accumulation of nanovaccines in B-cell zones,amplifying antigen-specific cytotoxic T lymphocyte responses and immunoglobulin G antibody expression in draining lymph nodes.ADN also generates systemic immune responses by causing immune memory and preventing T-cell anergy in the spleen.Further supported by evoking effective antitumor responses and high-level antiviral antibodies in mice,ADN provides a simple yet versatile platform for advanced nanovaccination.
文摘An immunostimulatory factor was identified to be secreted by antigen-pulsed maorophages. This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo. Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a genetically-restricted antigen specific factor (ASF). The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-pulsed maorophages with T lymphocytes, and then spleen cells, and finally the TNP-coated sheep red blood cells.
文摘The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota. Inflammatory bowel disease (IBD) involves a breakdown in tolerance towards the microbiota. Dendritic cells (DC), macrophages (MΦ) and B-cells are known as professional antigen-presenting cells (APC) due to their specialization in presenting processed antigen to T-cells, and in turn shaping types of T-cell responses generated. Intestinal DC are migratory cells, unique in their ability to generate primary T-cell responses in mesenteric lymph nodes or Peyer’s patches, whilst MΦ and B-cells contribute to polarization and differentiation of secondary T-cell responses in the gut lamina propria. The antigen-sampling function of gut DC and MΦ enables them to sample bacterial antigens from the gut lumen to determine types of T-cell responses generated. The primary function of intestinal B-cells involves their secretion of large amounts of immunoglobulin A, which in turn contributes to epithelial barrier function and limits immune responses towards to microbiota. Here, we review the role of all three types of APC in intestinal immunity, both in the steady state and in inflammation, and how these cells interact with one another, as well as with the intestinal microenvironment, to shape mucosal immune responses. We describe mechanisms of maintaining intestinal immune tolerance in the steady state but also inappropriate responses of APC to components of the gut microbiota that contribute to pathology in IBD.
基金Supported by Grants from the BioGreen 21 Program, Rural Development Administration (PJ007054)Regional Technology Innovation Program of the MOCIE (RTI05-01-01)Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (A080588-20)
文摘AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cell line(Raw 264.7),mouse primary antigen-presenting cells(APCs,MHCII+) and CD11c+dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively.To confirm the anti-inflammatory effects of cinnamon extract in vivo,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression prof iles in inflamed tissue.RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells(DCs) by suppressing expression of co-stimulatory molecules(B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase(COX)-2.Cinnamon extract induced regulatory DCs(rDCs) that produce low levels of pro-inflammatory cytokines [interleukin(IL)-1β,IL-6,IL-12,interferon(IFN)-γ and tumor necrosis factor(TNF)-α] while expressing high levels of immunoregulatory cytokines(IL-10 and transforming growth factor-β).In addition,rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines(IL-1β,IFN-γ and TNF-α),while enhancing IL-10 levels.CONCLUSION:Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10+ regulatory T cells.
基金supported by grants from the National Key Basic Research Programs(2001CB510007)National Natural Science Foundation of China(30371303).
文摘Systemic lupus erythematosus （SLE） is a typical autoimmune disease involving multiple systems and organs. Ample evidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This study was undertaken to investigate the mechanisms of interaction between antigen presenting cells （APCs） and an autoreactive T cell （ATLI） clone obtained from lupus-prone BXSB mice. ATLI cells, either before or after 7-ray irradiation, were able to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able to stimulate the proliferation of resting ATL 1 cells at a responder/stimulator （R/S） ratio of 1/2.5. Dendritic cells （DCs） were much more powerful stimulators for ATLI cells on a per cell basis. The T cell stimulating ability ofmacrophages and B cells, but not DCs, was sensitive to T-ray irradiation. Monoclonal antibodies against mouse MHC-Ⅱ and CD4 were able to block DC-mediated stimulation of ATL 1 proliferation, indicating cognate recognition between ATL 1 and APCs. Our data suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotal role in keeping the momentum of autoimmune responses leading to autoimmune diseases.
文摘Nanoparticles represent a heterogeneous collection of materials,whether natural or synthetic,with dimensions aligning in the nanoscale.Because of their intense manifestation with the immune system,they can be harvested for numerous bio-medical and biotechnological advancements mainly in cancer treatment.This review article aims to scrutinize various types of nanoparticles that interact differently with immune cells like macrophages,dendritic cells,T lymphocytes,and natural killer(NK)cells.It also underscores the importance of knowing how nanoparticles influence immune cell functions,such as the production of cytokines and the presentation of antigens which are crucial for effective cancer immunotherapy.Hence overviews of bio-molecular mechanisms are provided.Nanoparticles can improve antigen presentation,boost T-cell responses,and overcome the immunosuppressive tumor environment.The regulatory mechanisms,signaling pathways,and nanoparticle characteristics are also presented for a comprehensive understanding.We review the nanotechnology platform options and challenges in nanoparticlesbased immunotherapy,from an immunotherapy perspective including precise targeting,immune modulation,and potential toxicity,as well as personalized approaches based on individual patient and tumor characteristics.The development of emerging multifunctional nanoparticles and theranostic nanoparticles will provide new solutions for the precision and efficiency of cancer therapies in next-generation practice.
文摘The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive carrier state,chronic hepatitis,cirrhosis,hepatocellular carcinoma,to liver failure,depending on the success or failure of immune response to HBV.Genome-wide association studies(GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits.In this review,we discuss GWAS for persistence of HBV infection,antibody response to hepatitis B vaccine,and HBV-related advanced liver diseases.HBV persistence is associated with multiple genes with diverse roles in immune mechanisms.The strongest associations are found within the classical human leukocyte antigen(HLA) genes,highlighting the central role of antigen presentation in the immune response to HBV.Associated variants affect both epitope binding specificities and expression levels of HLA molecules.Several other susceptibility genes regulate the magnitude of adaptive immune responses,determining immunity vs tolerance.HBV persistence and nonresponse to vaccine share the same risk variants,implying overlapping genetic bases.On the other hand,the risk variants for HBV-related advanced liver diseases are largely different,suggesting different host-virus dynamics in acute vs chronic HBV infections.The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.
基金This work was supported by the National Natural Science Foundation of China,Nos.81671240(to SZZ),81560220(to GHL)the Youth Science Foundation of Jiangxi Province of China,No.20151BAB215014(to GHL)Health and Family Planning Commission of Jiangxi Province of China,No.20195109(to GHL)。
文摘The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurrence and development of Parkinson’s disease.However,it remains unclear whether oxidative stress induces Parkinson’s disease through the MHC-I pathway.In the present study,polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium(MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease mouse model.The findings revealed that MHC-I was expressed in both models.To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells,immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8(CD8)+T cell infiltration in the substantia nigra of MPTP-treated mice.The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+T cells.Moreover,in MPTP-induced Parkinson’s disease model mice,the genetic knockdown of endogenous MHC-I,which was caused by injecting specific adenovirus into the substantia nigra,led to a significant reduction in CD8+T cell infiltration and alleviated dopaminergic neuronal death.To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation,the expression of PTEN-induced kinase 1(PINK1)was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA(siRNA),and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells.Taken together,MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation,thus rendering dopaminergic neurons susceptible to immune cells and degeneration.This may be one of the mechanisms of oxidative stress-induced Parkinson’s disease,and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation.All animal experiments were approved by the Southern Medical University Ethics Committee(No.81802040,approved on February 25,2018).
基金This work was supported by grants from the Chinese Ministry of Science and Technology National Major Scientific Research Program(2015CB943200)the Key Project Grant from the National Natural Science Foundation of China(31330027)+1 种基金the National Basic Research Program of China(2015CB553800)the Tsinghua Science Foundation(20111080963).
文摘The role of the p38 signaling pathway in the innate and adaptive immune responses has been well documented,especially in inflammatory cytokine production by dendritic cells(DCs).However,whether the p38 signaling pathway affects the important antigen(Ag)presentation function of DCs remains largely unknown.In this study,we reported that the deletion of p38αresulted in an impaired cross-presentation ability of CD8^(+) conventional DCs(cDCs)and a reduction in the direct presentation ability of CD8−cDCs ex vivo.Further study revealed that p38αhad a crucial role in Ag processing by CD8^(+) cDCs but did not affect the Ag uptake or co-stimulation of T cells.Moreover,p38αdeficiency led to reduced cross-priming of T cells in vivo.The production of the IL-12p40 and IL-12p70 cytokines by p38α-deficient cDCs was also significantly reduced.Our study identified a new role for p38αin modulating the important antigen cross-presentation function of DCs.
基金supported by the National Natural Science Foundation of China(Nos.81901878,U1804183,and 82202318)Key Scientific Research Project(Education Department of Henan Province,China,20HASTIT049)China Postdoctoral Science Foundation(2019M662553,2020T130611,and 2022TQ0310)。
文摘Activating humoral and cellular immunity in lymph nodes(LNs)of nanoparticle-based vaccines is critical to controlling tumors.However,how the physical properties of nanovaccine carriers orchestrate antigen capture,lymphatic delivery,antigen presentation and immune response in LNs is largely unclear.Here,we manufactured gold nanoparticles(AuNPs)with the same size but different shapes(cages,rods,and stars),and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas.Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes.On lymphatic delivery,both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention.A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity,which is mediated by CD4^(+)T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study.Interestingly,cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8^(+)T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study.These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs,and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.
文摘Objective: To study the effects of hyperbaric air exposure on the functions of peritoneal macrophages of mice. Methods: Forty-eight mice were equally randomized to 6 groups: (1) normal air group (NA); (2) hyperbaric air group 1 (HA1); (3) hyperbaric air group 2 (HA2); (4) hyperbaric air group 3 (HA3); (5) hyperbaric oxygen group (HO);(6) hyperbaric nitrogen group (HN). Every group was exposed to corresponding pressure for 60 min, twice a day for 3 d. Peritoneal macrophages were obtained at the corresponding time to observe the changes of phagocytosis, acid phos-phatase, antigen presentation function and the produce of NO and TNF-α. Results: Compared with those in NA group, the activity of phagocytosis, acid phosphatase, antigen presentation function and the produce of NO and TNF-a were markedly inhibited in hyperbaric oxygen group and hyperbaric air group 1 ( P < 0.05, P < 0.01) and they changed little in HN group. These changes could disappear in 3 - 5 d. Conclusion: The functions of mice peritoneal macrophages were obviously inhibited in simulated air diving environment and hyperoxia may play an important role in it.
文摘Background and Objectives Autoimmune reaction may play an important role in the pathogenesis and progress in virus myocarditis. Dendritic cells are the initiators of immune reaction to foreign antigens and are considered to be key players in the induction and maintenance of autoimmune reactions. This study was undertaken to investigate the role of DC in mice with virus myocarditis. Methods and Results Fifty Balb/c mice were injected Coxsackie B3 virus to induce myocarditis and ten mice were injected culture liquid as control group. The hearts of virus - infected mice were harvested on day 3, 7, 14, 28 after the injection. All the hearts were sliced to do HE staining, MHC Ⅱ antigen and S - 100 protein immunohistochemical staining. The inflammation response and expression of MHC Ⅱ antigen and S - 100 protein positive stained cells were observed. The MHC Ⅱ antigen positive score were 1.42±0.95, 2.24 ±1. 00, 3. 23± 1. 16, 2. 58 ± 1. 05 respectively in group 3d, 7 d, 14 d, 28 d, which were significant different from control group(0. 50 ±0.75, P <0. 05). The S-100 positive staining cells in control group was 3. 2±1. 0. And the numbers were 6. 7 ± 1. 4 , 16. 4 ± 2. 5 , 21. 2±3. 3 , 13. 4 ± 2. 3 respectively in group 3 d, 7 d, 14 d, 28 d, and there were significant differences compared with the control group ( P < 0. 01) . Conclusions Immune reaction was involved in the pathogenesis in Coxsackie B3 virus - induced myocarditis in mouse, and dendritic cell might play an important role in the immune reaction.
