Journal of immunology最新文献

Genomic organization of the TCRα locus and essential roles of αβ T cells in antibacterial immunity in Nile tilapia. 尼罗罗非鱼TCRα基因座的基因组结构及αβ T细胞在抗菌免疫中的重要作用

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkag038

Ming Geng, Kang Li, Jiansong Zhang, Yuying Zheng, Haokai Chen, Qiqi Jiang, Jialong Yang, Xiumei Wei

{"title":"Genomic organization of the TCRα locus and essential roles of αβ T cells in antibacterial immunity in Nile tilapia.","authors":"Ming Geng, Kang Li, Jiansong Zhang, Yuying Zheng, Haokai Chen, Qiqi Jiang, Jialong Yang, Xiumei Wei","doi":"10.1093/jimmun/vkag038","DOIUrl":"https://doi.org/10.1093/jimmun/vkag038","url":null,"abstract":"T cells utilize diverse T cell receptors (TCRs) to recognize antigenic peptides and mediate adaptive immunity. However, the organization and function of αβ T cells in early vertebrates remain poorly understood. Here, we systematically characterized the TCRα locus and αβ T cell responses in Nile tilapia (Oreochromis niloticus) during Edwardsiella piscicida infection. Genomic analysis revealed that the TCRα locus in Nile tilapia exhibits a distinctive Vα(61)-Jα(82)-Cα(1)-Vα(65) structure with conserved synteny in the flanking regions, while the constant region retains essential residues for TCR/CD3 complex assembly. We further generated monoclonal antibody against tilapia TCRα and TCRβ and confirmed their coexpression by the majority of CD3ε+ T cells, validating these cells as bona fide αβ T cells. Functional assays showed that CD3ε/CD28 monoclonal antibody stimulation induced robust αβ T cell activation, as evidenced by enhanced phosphorylation of S6, NF-κB, and ERK1/2, together with vigorous cellular proliferation. In vivo, E. piscicida infection triggered a pronounced expansion of αβ T cells, indicating their active involvement in antibacterial immunity. Importantly, depletion of αβ T cells severely impaired pathogen clearance and significantly increased host mortality. Together, these findings elucidate the indispensable role of αβ T cells in the antibacterial immunity of teleosts and provide critical insights into the functional mechanisms of adaptive immunity in early vertebrates.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ischemia-free liver transplantation alleviates liver transplant injury caused by CD69+CD103-CD8+T cells by regulating HIF-2α expression. 无缺血肝移植可通过调节HIF-2α表达减轻CD69+CD103-CD8+T细胞所致的肝移植损伤。

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkag005

Zhitao Chen, Jiahao Ji, Yuqi Dong, Dongmei Ye, Yu Jia, Yiwen Guo, Yingqian Zhong, Wenjing He, Yifang Gao, Xiaoshun He

{"title":"Ischemia-free liver transplantation alleviates liver transplant injury caused by CD69+CD103-CD8+T cells by regulating HIF-2α expression.","authors":"Zhitao Chen, Jiahao Ji, Yuqi Dong, Dongmei Ye, Yu Jia, Yiwen Guo, Yingqian Zhong, Wenjing He, Yifang Gao, Xiaoshun He","doi":"10.1093/jimmun/vkag005","DOIUrl":"https://doi.org/10.1093/jimmun/vkag005","url":null,"abstract":"In this study, we investigate the mechanisms by which ischemia-free liver transplantation (IFLT) mitigates ischemia-reperfusion injury (IRI) and identify key therapeutic targets. Clinical data from 200 patients were collected to evaluate perioperative recovery and overall outcomes. Liver tissues were obtained from donors at the preprocurement, end-of-preservation, and postperfusion stages. Gene expression profiles were examined using single-cell transcriptomic analysis. Phenotypic and functional characteristics were evaluated using flow cytometry, and protein expression was assessed using immunofluorescence, immunohistochemistry, and enzyme-linked immunosorbent assay. Animal models of IRI were employed to examine the effects of HIF-2α inhibition in vivo. PT-2385 was administered to inhibit HIF-2α, and 100 µg of anti-mouse CD8α monoclonal antibody was injected to deplete CD8+ T cells. Patients in the IFLT group exhibited a lower incidence of early allograft dysfunction and a higher 1-yr survival rate. Differential gene expression analysis of IRI-related genes in 14 paired liver samples from conventional liver transplantation revealed significant upregulation of HIF-2α in postreperfusion tissues, predominantly expressed in CD69+CD103-CD8+ T cells. The up-regulated genes were enriched in TNF-related signaling pathways. Inhibition of HIF-2α reduced the number of CD69+CD103-CD8+ T cells and alleviated liver injury in vivo. In IFLT, genes in this pathway were not significantly upregulated. Under HIF-2α stimulation, CD69+CD103-CD8+ T cells exacerbate organ and tissue injury through TNF-related signaling. In IFLT, the absence of significant pathway upregulation suggests effective prevention of IRI.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Caspase-8 mediates E. coli-induced cell death and innate immune responses. Caspase-8介导大肠杆菌诱导的细胞死亡和先天免疫反应。

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkag037

Zhuodong Chai, Yuqi Zhou, Ling Yang, Yan Zhang, Sukria Hossain, Guoying Zhang, Jiaqian Qi, Ziran Zhang, Toshihiko Shiroishi, Yinan Wei, Zhenyu Li

{"title":"Caspase-8 mediates E. coli-induced cell death and innate immune responses.","authors":"Zhuodong Chai, Yuqi Zhou, Ling Yang, Yan Zhang, Sukria Hossain, Guoying Zhang, Jiaqian Qi, Ziran Zhang, Toshihiko Shiroishi, Yinan Wei, Zhenyu Li","doi":"10.1093/jimmun/vkag037","DOIUrl":"https://doi.org/10.1093/jimmun/vkag037","url":null,"abstract":"Escherichia coli (E. coli) is a leading cause of invasive bacterial infections in humans. Pathogenic E. coli is not only the major etiological agent of enteric/diarrheal disease and urinary tract infections, but also among the most common causes of sepsis and meningitis. Caspase-8 is known to regulate apoptotic and pyroptotic cell death in response to bacterial and viral infections. Here we demonstrate that caspase-8 plays a critical role in E. coli-induced macrophage apoptosis in vitro and in regulating immune response and host death in vivo. Incubation of mouse bone marrow derived macrophages (BMDMs) with an E. coli K1 strain CE10 triggered robust cell death, which is independent of the NAIP/NLRC4/caspase-1/GSDMD pathway. CE10 stimulation induced caspase-8 activation, and macrophages deficient in caspase-8 and RIPK3, but not RIPK3 alone, were protected from CE10-induced cell death. In an intraperitoneal injection sepsis model, E. coli-induced IL-1β, TNF-α, and IL-6 production was markedly reduced in caspase-8-/-/RIPK3-/- mice, compared with RIPK3-/- or wild type mice. Accordingly, the survival rate was significantly improved in caspase-8-/-/RIPK3-/- mice. Moreover, caspase-8 deficiency attenuated CE10-induced NF-κB activation and cytokine production in BMDMs. Together, our findings identify caspase-8 as a central mediator of E. coli-induced cell death, immune response, and establish its critical contribution to host mortality during E. coli infection.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ligation of TLR2, but not of TLR4 or other Toll-like receptors, induces neutrophil extracellular trap formation in humans. 结扎TLR2，而不是TLR4或其他toll样受体，可诱导人类中性粒细胞胞外陷阱的形成。

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkag079

Hugo Tshivuadi Mosha, Vanessa de Carvalho Oliveira, Olga Tatsiy, Abdelaziz Amrani, Patrick P McDonald

{"title":"Ligation of TLR2, but not of TLR4 or other Toll-like receptors, induces neutrophil extracellular trap formation in humans.","authors":"Hugo Tshivuadi Mosha, Vanessa de Carvalho Oliveira, Olga Tatsiy, Abdelaziz Amrani, Patrick P McDonald","doi":"10.1093/jimmun/vkag079","DOIUrl":"https://doi.org/10.1093/jimmun/vkag079","url":null,"abstract":"Neutrophils are usually the first cells recruited to sites of injury or infection where they mount antimicrobial responses, including the release of neutrophil extracellular traps (NETs). Toll-like receptors play a major role in the recognition of pathogen-associated molecular patterns and all but TLR3 are expressed in neutrophils. Numerous studies have reported that LPS can trigger NET formation; in nearly all cases, however, the ligand was not purified enough to target only TLR4. There also exist isolated reports on the ability of other TLRs to induce NETs. Here we comprehensively revisited the issue of TLR-elicited NET generation using ultrapure ligands. We now report that in humans, NETs are only induced following TLR2 ligation whereas engagement of other TLRs is ineffective (despite eliciting other cellular responses). A widely used (but incompletely purified) LPS preparation potently induced NET generation by binding TLR4, TLR2, and possibly other receptors, confirming previous data from other groups. By contrast, murine NETs are formed upon either TLR2 or TLR4 engagement. Mechanistically, TLR2-triggered NET formation is controlled by signaling kinases that are mobilized early (TAK1, MEK, p38 MAPK) or belatedly (Syk, PI3K, PLCγ2); acts through endogenous factors that bind the RAGE receptor; and involves PAD4 as well as endogenous reactive oxygen species, whereas elastase is dispensable. Conversely, we provide evidence that TLR4 negatively regulates NET formation in humans. Our study shows the surprisingly restricted repertoire of TLRs that can elicit NET formation in humans, and further illustrates how this emblematic neutrophil response differs between humans and rodents.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The seminal effect of one-two IFNGR1 genetic punch from 30 years ago. 从30年前开始的一对IFNGR1基因冲击的开创性影响。

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkaf356

Dusan Bogunovic

引用次数: 0

Role of Ca2+-activated KCa3.1 potassium channel in CAR T cell effector function. Ca2+激活的KCa3.1钾通道在CAR - T细胞效应功能中的作用。

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkag078

Vivien Jusztus, Márton Hajdu, Péter Horváth, György Panyi, Péter Hajdu

引用次数: 0

HIF-1α impairs NK cell differentiation-maturation and cytotoxicity in myelodysplastic syndrome via JAK1/STAT5/SOCS2 pathway. HIF-1α通过JAK1/STAT5/SOCS2通路影响骨髓增生异常综合征的NK细胞分化成熟和细胞毒性

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkag059

Shujuan Xu, Yixiang Jiang, Shengtao Wang, Beili Chen, Wenyuan Lin, Fang Jiang, Xianyi Wu, Rongfang Tang, Yuwei Nie, Tongtong Chen, Xiaotao Wang

{"title":"HIF-1α impairs NK cell differentiation-maturation and cytotoxicity in myelodysplastic syndrome via JAK1/STAT5/SOCS2 pathway.","authors":"Shujuan Xu, Yixiang Jiang, Shengtao Wang, Beili Chen, Wenyuan Lin, Fang Jiang, Xianyi Wu, Rongfang Tang, Yuwei Nie, Tongtong Chen, Xiaotao Wang","doi":"10.1093/jimmun/vkag059","DOIUrl":"https://doi.org/10.1093/jimmun/vkag059","url":null,"abstract":"Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid neoplasms characterized by treatment difficulties and a propensity to progress to acute myeloid leukemia. Impaired natural killer (NK) cell surveillance is a hallmark of MDS, yet the underlying molecular mechanisms remain poorly understood. This study aims to elucidate the mechanism by which HIF-1α regulates NK cell differentiation disorders and its impact on NK cell cytotoxicity in MDS. Flow cytometry was employed to compare HIF-1α expression and NK cell differentiation between wild-type and NUP98/HOXD13 (NHD13) mice. Our results demonstrated a significant increase in HIF-1α expression in the bone marrow and peripheral blood of MDS mice, accompanied by a notable decrease in immature NK cell subsets and activating receptors (NKG2D, NKp44, and DNAM-1). Overexpression of HIF-1α in human NK cells or pharmacological stabilization with CoCl2 inhibits the differentiation into mature NK cells, suppresses the expression of degranulation molecules such as Granzyme B, and impairs NK cell cytotoxicity. Western blot analysis indicated that HIF-1α regulates NK cell differentiation and function via the JAK1/STAT5/SOCS2 signaling pathway. Collectively, these findings suggest that the hypoxic microenvironment in MDS enhances HIF-1α expression, which subsequently impairs NK cell maturation and inhibits their cytotoxicity. Targeting HIF-1α may delay MDS progression by enhancing NK cell function via the JAK1/STAT5/SOCS2 signaling pathway.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The dual role of peritoneal cavity B cells in the activation of antitumor T cells. 腹膜腔B细胞在激活抗肿瘤T细胞中的双重作用。

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkag058

Tetsuya Mochizuki, Yuka Tanaka, Ryuta Ide, Hideki Ohdan

{"title":"The dual role of peritoneal cavity B cells in the activation of antitumor T cells.","authors":"Tetsuya Mochizuki, Yuka Tanaka, Ryuta Ide, Hideki Ohdan","doi":"10.1093/jimmun/vkag058","DOIUrl":"https://doi.org/10.1093/jimmun/vkag058","url":null,"abstract":"Peritoneal cavity (PerC) B cells can be classified into distinct subpopulations; however, their differential antigen-presenting capabilities and roles in antitumor immune responses remain largely unexplored. This study aimed to elucidate the properties of PerC B cell subpopulations in antitumor immune responses by using ovalbumin (OVA) peptides as neoantigen mimics and employing OT-I mice, which express a transgenic T cell receptor specific to OVA peptides. We found that OVA-pulsed PerC B cells effectively stimulated CD8+ T cell proliferation, although their antigen-presenting capacity was lower than that of splenic B cells. Subpopulation analysis revealed that CD11b+CD80+ and CD11b-CD80+ B cells produced high levels of interleukin 10 (IL-10), contributing to immunosuppressive effects. Blocking IL-10 significantly enhanced T cell proliferation and cytotoxicity, whereas PD-L1/PD-L2 blockade had no significant impact. The CD8+ T cell response in OT-I mice, stimulated by bone marrow-derived dendritic cells (BMDCs) that had phagocytosed OVA, was dose-dependently suppressed by OVA-pulsed peritoneal B cells. In an in vivo tumor model using Rag2-/- mice, co-administration of OVA-pulsed PerC B cells transiently suppressed tumor growth at lower B: T ratios but promoted tumor progression at higher B: T ratios. IL-10 knockdown in PerC B cells further enhanced tumor suppression. These findings suggest that PerC B cells exhibit a dual role in antitumor immunity, modulating CD8+ T cell responses in a density-dependent manner. While they can function as antigen-presenting cells to enhance T cell activation, their IL-10-mediated immunosuppressive properties can dampen antitumor responses. Understanding this balance may provide insights for optimizing B cell-based immunotherapies.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-ligand-binding TLR20.2 and dsRNA-binding TLR20.3 form heterodimer for synergistic antiviral response in grass carp. 非配体结合的TLR20.2和dsrna结合的TLR20.3形成异源二聚体，协同草鱼抗病毒应答。

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkag040

Pengxu Wang, Shijie Wang, Ningxia Xiong, Jingjing Zhang, Maolin Lv, Chunrong Yang, Jianguo Su

{"title":"Non-ligand-binding TLR20.2 and dsRNA-binding TLR20.3 form heterodimer for synergistic antiviral response in grass carp.","authors":"Pengxu Wang, Shijie Wang, Ningxia Xiong, Jingjing Zhang, Maolin Lv, Chunrong Yang, Jianguo Su","doi":"10.1093/jimmun/vkag040","DOIUrl":"https://doi.org/10.1093/jimmun/vkag040","url":null,"abstract":"TLR20 is a teleost-specific TLR member. However, its species distribution, biological function, and underlying mechanism remain largely unknown. In this study, we systematically retrieved the TLR20 species distribution and found only a few teleosts contain different TLR20 variants, especially in Cyprinidae. Subsequently, we employed an economically important model, grass carp (Ctenopharyngodon idella) with three TLR20 variants, to investigate the functional characterizations and mechanisms of TLR20. Ci-TLR20.1 localizes to both early endosomes and lysosomes, whereas Ci-TLR20.2/3 exclusively localize to lysosomes. Further, we found that Ci-TLR20.1 cannot form homodimer and heterodimers with Ci-TLR20.2/3, but Ci-TLR20.2/3 can form homodimers and heterodimer. Ci-TLR20.3 can directly bind to the dsRNA analog poly (I:C) via key residues F27, Q630, and T631. Although Ci-TLR20.2 lacks this ability, the reverse mutation I26L+R630Q confers dsRNA binding ability. Interestingly, Ci-TLR20.2/3 can also respond to PGN stimulation. However, they cannot directly bind PGN. Ci-TLR20.2/3 recruit MyD88 as an adaptor independent of the conserved proline residue in BB loop, significantly activating IFN, NF-κB and AP-1 pathways. Functionally, overexpression of Ci-TLR20/3, or their combination significantly inhibits grass carp reovirus (GCRV) replication. Correspondingly, knockdown of these receptors facilitates viral infection. In vivo knockdown of Ci-TLR20.2/3 reduces the survival rate of grass carp following GCRV infection, exacerbates virus-induced tissue damage, and suppresses complement C3, SOD, IFN1, and antiviral effector Mx2. We also found that Ci-TLR20.2 and Ci-TLR20.3 synergistically defend against viral infection in vitro and in vivo. These findings provide novel insights into the functional divergence and synergistic effects of teleost-specific TLR20 in antiviral defense.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deficiency of microRNA-10a in CD4+ T cells protects against intestinal infection through mitochondrial oxidation-IL-22 pathway. CD4+ T细胞缺乏microRNA-10a通过线粒体氧化- il -22途径保护肠道感染。

IF 3.4 3区医学

Journal of immunology Pub Date : 2026-04-15 DOI: 10.1093/jimmun/vkag089

Wenjing Yang, Tianming Yu, Suxia Yao, Yingzi Cong

{"title":"Deficiency of microRNA-10a in CD4+ T cells protects against intestinal infection through mitochondrial oxidation-IL-22 pathway.","authors":"Wenjing Yang, Tianming Yu, Suxia Yao, Yingzi Cong","doi":"10.1093/jimmun/vkag089","DOIUrl":"https://doi.org/10.1093/jimmun/vkag089","url":null,"abstract":"Interleukin 22 (IL-22) produced by CD4+ T cells plays an important role in regulating intestinal immune responses during inflammation and infection, but the mechanisms controlling IL-22 expression in T cells remain incompletely understood. MicroRNA-10a (miR-10a) is known to regulate CD4+ T-cell function, but its role in IL-22 production has not been defined. Here, using mouse CD4+ T cell-specific miR-10a knockout models, we examined how miR-10a regulates IL-22 expression and the underlying metabolic mechanisms. MiR-10a deficiency led to increased IL-22 production in CD4+ T cells both in vitro and in vivo, under steady and inflammatory conditions. CD4+ T cell-specific miR-10a knockout mice were resistant to Citrobacter rodentium infection, and the protection was abolished when blocking the IL-22 pathway in mice. Mechanistically, miR-10a-deficient CD4+ T cells exhibited increased mitochondrial oxidative metabolism and membrane potential. Pharmacologic inhibition of mitochondrial complex III with antimycin A suppressed the enhanced IL-22 production in miR-10a-deficient T cells. We further identified Uqcrq, a subunit of mitochondrial complex III, as a direct target of miR-10a, and loss of Uqcrq suppressed IL-22 production in CD4+ T cells. Together, these findings identify miR-10a as a T cell-intrinsic regulator of mitochondrial oxidative metabolism that constrains IL-22 production in the intestine.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0