Cellular &Molecular Immunology最新文献

{"title":"BCR signal strength governs VH gene replacement in peripheral B cells","authors":"Monika Vashisht, Huaibin Ge, Karen Siddoway, Jessy John, Harlie A. McKelvey, Rui Dong, Mohammad A. I. Al-Hatamleh, Alexandra Krinsky, Vince Popolizio, Alondra M. Ware, Gero Knittel, Hans Christian Reinhardt, Zhangguo Chen, Jing H. Wang","doi":"10.1038/s41423-026-01473-0","DOIUrl":"10.1038/s41423-026-01473-0","url":null,"abstract":"Generated by stochastic V(D)J recombination, unique B-cell receptors (BCRs) consist of IgH and IgL chains, recognize antigens, and serve as distinct barcodes to identify each individual B cell. Once a B-cell acquires its BCR, does it maintain its identity, or does a peripheral B-cell ever rearrange its BCR again? Under what circumstances a peripheral B-cell would undergo secondary V(D)J recombination at its Igh locus, termed VH gene replacement (VHR), remains poorly understood. Using hen egg lysozyme (HEL) BCR knock-in mice, we observed that when the BCR cannot bind to any foreign or self-antigen, peripheral B cells upregulate the expression of the VDJ recombinase RAG-1 and undergo VHR to acquire new BCRs and become non-HEL-binding. TRAF3 deficiency increased the frequency of VHR-experienced B cells and predisposed them to abnormal oligoclonal expansion by preventing B cells from dying from RAG-initiated DNA double-stranded breaks in an NF-κB2-dependent manner. Engaging the HEL BCR or inhibiting proximal BCR signaling modulated RAG-1 expression. The frequency of VHR was substantially inhibited by enhanced BCR signaling caused by a gain-of-function mutant allele of Cd79b, a signaling component of the BCR complex. We conclude that BCR signaling strength influences the probability of a given B-cell undergoing VHR. Furthermore, signaling molecules such as TRAF3 can serve as nonclassical checkpoints to maintain B-cell genome stability during VHR. Our studies provide fundamental insights into the mechanisms underlying the dynamic regulation of antigen receptor identity in peripheral B cells, with implications for immune tolerance and B-cell homeostasis. Our studies reveal novel mechanisms of genomic instability in VHR-experienced peripheral B cells and provide fundamental insights into the conditions under which B cells alter their identity via VHR, as well as the regulatory mechanisms governing the VHR process.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 11","pages":"1473-1490"},"PeriodicalIF":23.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geranylgeranylation is required for B-cell proliferation and plasma cell survival implications for autoimmune therapy","authors":"Lai Wang, Haoyuan Yin, Jiayi Lu, Shangru Li, Shumei Cao, Jiao Jiang, Junhui Wu, Qilin Li, Xiaoyu Su, Wenrui Li, Meiling Zheng, Ming Zhao, Qianjin Lu","doi":"10.1038/s41423-026-01472-1","DOIUrl":"10.1038/s41423-026-01472-1","url":null,"abstract":"Tissue-resident long-lived plasma cells, whose current therapies fail to effectively eliminate them, are now recognized as key factors in refractory and relapsed autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we discovered that the most commonly used cholesterol-lowering drugs in clinical practice, particularly lipophilic statins, can deplete antibody-secreting cells (ASCs) by triggering endoplasmic reticulum stress (ERS)-mediated apoptosis. Supplementation with geranylgeranyl pyrophosphate (GGPP) completely counteracted the effects of statins on ASCs. Targeting geranylgeranyltransferase type II (GGTase Ⅱ) downstream of GGPP through the use of 3-PEHPC, a chemical inhibitor of GGTase Ⅱ, replicated the destructive effects of statins on ASCs. Additionally, by generating mice with B-cell-specific deletion of Rabggta, which encodes RABGGTA, the specific subunit of GGTase II, we further demonstrated that GGTase II is critical for antibody responses, as well as for the generation of germinal centers, memory B cells, and bone marrow plasma cells. Mechanistically, GGTase II is essential for B-cell activation and proliferation and for protecting B cells from cell death triggered by mitogenic signals. Furthermore, GGTase Ⅱ deficiency in B cells impeded disease progression in lupus-like mice. Both 3-PEHPC and atorvastatin were effective at alleviating disease activity in these lupus-like models, resulting in significant depletion of ASCs. In conclusion, our study highlights GGTase II as a potential therapeutic target for autoimmune diseases and highlights the promising role of statins in their treatment.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 11","pages":"1457-1472"},"PeriodicalIF":23.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR signaling instructs divergent metabolic reprogramming and functional fates in αβ and γδ T cells","authors":"Xiomar E. Bustos, Leticia Tordesillas, Elena Martinez Planes, Miguel G. Fontela, Sebastian Snedal, Renata Ariza Marques Rossetti, Victoria Izumi, Bin Fang, John M. Koomen, Eric A. Welsh, Patrick Hwu, Daniel Abate-Daga","doi":"10.1038/s41423-026-01475-y","DOIUrl":"10.1038/s41423-026-01475-y","url":null,"abstract":"γδ T-cell-based immunotherapies have become relevant as alternatives to conventional αβ T-cell products, with preclinical data demonstrating tumor burden reduction and the mitigation of tumor-induced tissue damage. Given that most CAR constructs have been optimized for αβ T cells, we hypothesized that distinct T-cell types may require tailored CAR architectures to achieve optimal function. To test this hypothesis, we conducted a systematic comparative analysis of γδ and αβ T cells transduced with a second-generation PSCA-targeting CAR (PSCA-8t28z). We found that although γδ and αβ CAR-T cells exhibit comparable levels of cytotoxicity, they differ phenotypically. Through a system-level phosphoproteomic analysis, we identified 307 phosphosites whose abundance differed between γδ and αβ CAR-T cells. Pathway enrichment analysis placed glycolysis/gluconeogenesis and TCR signaling within the top significantly overrepresented signaling networks. The results of functional validation studies confirmed that γδ CAR-T cells have lower glycolytic and oxidative phosphorylation capacity than αβ-CAR-T cells do and weaker activation of activator protein 1 (AP-1). Notably, we identified thioredoxin-interacting protein (TXNIP) as a potential actionable target to enhance γδ CAR-T-cell metabolism. Finally, we designed a new synthetic costimulatory receptor that potentiates AP-1 activation, resulting in improved in vivo persistence. These results highlight the fundamental biological differences between γδ and αβ T cells and support the development of cell type-specific receptor engineering strategies to maximize γδ CAR-T-cell function and therapeutic benefit.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 11","pages":"1441-1456"},"PeriodicalIF":23.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-026-01475-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells","authors":"Xiangming Liu, Nan Li, Yumeng Chen, Zijun Xie, Tao Huang, Shijie Li, Xinxin Wang, Ruiqi Zhang, Xiaohong Yu, Huiqin Meng, Jingya Guo, Yang Liu, Yang-Xin Fu, Zaopeng Yang","doi":"10.1038/s41423-026-01467-y","DOIUrl":"10.1038/s41423-026-01467-y","url":null,"abstract":"Cytokines are powerful modulators of antitumor immunity, but their clinical use is limited by structural instability, short half-life, poor drug-like properties, and severe systemic toxicity. Antibody-based cytokine mimetics have recently emerged to activate immune cells in vitro, but whether these mimetics can overcome the shortcomings of cytokines and exert therapeutic efficacy in vivo remains unclear. Here, we engineered bispecific antibody-based IL-15 mimetics using immunized Alpaca-derived phage display coupled with AlphaFold3-assisted structural screening and comparative screening of multiple formats to identify tandem IL-15 mimetics with strong in vitro bioactivity. Importantly, tandem IL-15R agonistic bispecifics, which simultaneously engage IL-15Rβ and γc, clearly demonstrated antitumor activity in vivo. To better target tumor-infiltrating lymphocytes (TILs), we incorporated a high-affinity anti-TIGIT antibody to guide tandem IL-15Rβγ agonists. This tri-antibody design, αTIGIT-αIL-15Rβγ, resulted in a striking improvement in antitumor activity without detectable systemic toxicity even at high doses. Mechanistically, αTIGIT-αIL-15Rβγ enhanced CD8⁺ T effector function and expanded the number of intratumoral stem-like T cells. Our study highlights a strategy to use TIL-targeted cytokine mimetics to overcome the limitations of native cytokines and enable dose pairing with immune checkpoint blockade (ICB), offering a path toward safer and more effective cytokine immunotherapy.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 10","pages":"1355-1367"},"PeriodicalIF":23.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HnRNPK restrains memory precursor and plasma cell differentiation to control germinal center B-cell output","authors":"Jiayuan Li, Jing Wang, Silu Li, Changxu Chen, Chengyu Yang, Zhenya Liu, Xiaosu Ke, Zhuanhuai Wang, Bin Wang, Hui Li, Gui-Xin Ruan, Xijun Ou, Hengjun Huang","doi":"10.1038/s41423-026-01469-w","DOIUrl":"10.1038/s41423-026-01469-w","url":null,"abstract":"Germinal center (GC) B cells are critical for the production of long-lived plasma cells and high-affinity antibodies. Upon exiting the GC reaction, B cells differentiate into either memory B (MB) cells or plasma cells depending on affinity signals and transcription factor profiles. However, the underlying transcriptional and metabolic mechanisms regulating this fate decision remain poorly understood. Here, we generated mice with B and GC B-cell–specific knockout of heterogeneous nuclear ribonucleoprotein K (hnRNPK). We found that hnRNPK deletion partially impaired B-cell development and, more strikingly, markedly attenuated the GC B-cell response. The reduction in GC B-cell numbers was attributed to excessive differentiation of precursor MB cells and plasma cells during the GC reaction. Mechanistically, hnRNPK directly suppressed the expression of the key MB cell–associated transcription factors Hhex and Zfp318. Moreover, we observed that compared with CD25-negative GC B cells, CD25-positive GC B cells displayed elevated glycolytic gene expression and significantly increased glucose uptake. HnRNPK deficiency further upregulated glycolytic activity, promoted CD25 expression, and consequently enhanced plasma cell differentiation. Blocking IL‑2/CD25 signaling mitigated the excessive plasmablast differentiation induced by hnRNPK loss and rescued the GC defects in hnRNPK‑deficient mice. Together, these findings demonstrate that hnRNPK controls GC B-cell output by transcriptionally repressing the expression of the MB cell–differentiation factors Hhex and Zfp318 and by modulating the glycolysis‑CD25 regulatory axis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 10","pages":"1326-1342"},"PeriodicalIF":23.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p97-mediated proteostasis is a checkpoint for late-stage thymocyte positive selection","authors":"Ruixian Yu, Weihong Zhang, Yi Han, Wenjia Wang, Yan Meng, Pingping Nie, Cuiwei Zhang, Zaisheng Ye, Bin Yan, Zhaocai Zhou, Shi Jiao","doi":"10.1038/s41423-026-01466-z","DOIUrl":"10.1038/s41423-026-01466-z","url":null,"abstract":"AAA+ ATPase p97 is a central regulator of protein homeostasis, yet its role in late-stage thymocyte development remains undefined. Here, we demonstrate that T-cell-specific ablation of p97 in mice severely blocks the double-positive (DP) to single-positive (SP) transition, with a pronounced defect in CD8+ lineage commitment. Using both genetic deletion and acute pharmacological inhibition, we revealed a stage- and lineage-specific requirement for p97, with DP thymocytes being most sensitive to p97 loss. This failure in late-stage positive selection leads to intrathymic developmental arrest of immature DP cells and profound peripheral T-cell lymphopenia. Mechanistically, p97 deficiency results in the accumulation of ubiquitinated proteins, triggering the unfolded protein response and apoptosis in thymocytes. Furthermore, we identified a critical requirement for p97 in sustaining IL-7 receptor (IL-7R) expression and JAK signaling. Strikingly, pharmacological activation of JAK partially rescued SP thymocyte development in p97-deficient mice. Our findings establish p97-mediated protein homeostasis as a previously uncharacterized, cell-intrinsic checkpoint that is indispensable for late-stage positive selection by preventing proteostatic collapse and ensuring the fidelity of IL-7R signaling.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 10","pages":"1343-1354"},"PeriodicalIF":23.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the FOXP3–T-bet interaction to restore Treg stability in IFN-γ–driven autoimmunity","authors":"Weiqi Zhang, Xinnan Liu, Zhiyong Gu, Jiahang Xu, Zheng Bao, Rui Liang, Zhenran Xu, Dan Teng, Guojun Qu, Qianru Huang, Yi Lei, Feng Xie, Na Tian, Yichao Han, Siyuan Qiang, Hecheng Li, Guohua Li, Dan Li, Sulin Zhang, Song Guo Zheng, Zhi Liu, Shigang Yin, Mingyue Zheng, Feihong Luo, Xueyu Dai, Bin Li","doi":"10.1038/s41423-026-01468-x","DOIUrl":"10.1038/s41423-026-01468-x","url":null,"abstract":"Regulatory T-cell (Treg) stability is maintained by dynamic remodeling of the FOXP3 transcriptional complex, and disruption of this complex leads to Treg dysfunction and immune dysregulation. However, how specific FOXP3 mutations alter the dynamic remodeling of the FOXP3 complex and thereby contribute to pathogenic Treg reprogramming in IPEX syndrome remains unclear. Here, we demonstrate that predominant Th1 inflammation manifests in both FOXP3V408M IPEX patients and FOXP3V408M knock-in mice and reveal that the mutation intrinsically impairs Treg-mediated control of Th1 inflammation, revealing a distinct pathogenesis of this mutation in IPEX syndrome. Mechanistically, the V408M mutation disrupts the FOXP3–T-bet interaction, impairing the FOXP3-mediated restraint of T-bet-driven IFN-γ production and thereby contributing to increased Th1 inflammation. Using an AI-driven virtual screening approach, we identified a first-in-class small molecule, FM029, that directly binds to FOXP3 and reinforces its interaction with T-bet. FM029 strongly suppressed Treg-derived IFN-γ production and alleviated IFN-γ-driven tissue inflammation in both FOXP3V408M mice and an acute colitis model. Collectively, these findings establish the FOXP3–T-bet interaction as a central checkpoint that governs Treg stability and IFN-γ-driven Th1 pathology, providing a proof-of-concept that pharmacologic stabilization of the FOXP3–T-bet interaction can mitigate IFN-γ-driven immune disorders.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 10","pages":"1308-1325"},"PeriodicalIF":23.9,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death","authors":"Nanyang Xiao, Zexuan Lu, Destiny K. Cooper, Jueqi Chen","doi":"10.1038/s41423-026-01463-2","DOIUrl":"10.1038/s41423-026-01463-2","url":null,"abstract":"The NLRP3 inflammasome is a central signaling pathway of innate immunity that orchestrates host defense and inflammatory responses through the activation of proinflammatory cytokines and the induction of pyroptotic cell death. Accumulating evidence indicates that NLRP3 functions within an extensive network of innate immune and cell death pathways. Reciprocal interactions between NLRP3 and other pattern-recognition receptor pathways, including Toll-like receptors, DNA-sensing cGAS–STING signaling, and RNA-sensing RIG-I/MDA5–MAVS signaling, shape the magnitude and duration of inflammatory responses during pathogen infection. Moreover, substantial crosstalk exists between NLRP3 and other inflammasomes and programmed cell death pathways, reflecting the integrated nature of cellular stress and inflammatory signaling. In this review, we summarize recent advances in our understanding of the molecular mechanisms that mediate these interactions, focusing on shared signaling components, organelle dynamics, posttranslational modifications, and feedback regulatory circuits. We further discuss how these signaling networks contribute to infectious and inflammatory diseases and highlight key unanswered questions and emerging areas of investigation that may guide the development of therapies targeting inflammasome-associated pathologies.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 10","pages":"1194-1218"},"PeriodicalIF":23.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-026-01463-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Platelet-derived serotonin epigenetically programs macrophage alternative activation to orchestrate type 2 airway inflammation","authors":"Ru Tang, Guofang Xia, Ying Zhu, Jinhong Shen, Zhihan Liu, Song Mao, Jiayao Zhou, Yuelong Gu, Shilei Pu, Zhipeng Li, Hai Lin, Congfeng Xu, Hongqing Xu, Feng Zhang, Yongxu Zhao, Shankai Yin, Weitian Zhang, Feng Liu","doi":"10.1038/s41423-026-01465-0","DOIUrl":"10.1038/s41423-026-01465-0","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 10","pages":"1388-1388"},"PeriodicalIF":23.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-026-01465-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABTB1, as an E3 ubiquitin ligase, suppresses Th17 cell differentiation and mitigates autoimmune inflammation by promoting STAT3 ubiquitination and degradation","authors":"Fei Xu, Shuang Zhao, Yan Jiang, Xiaoping Li, Wenjun Wang, Ying Zhou, Yufeng Wang, Peijie Zhu, Yu Shao, Guodong Qiao, Jiamin Cai, Mengyao Sun, Jiaoyang Li, Chuangli Hao, Yi Yang, Jinping Zhang","doi":"10.1038/s41423-026-01464-1","DOIUrl":"10.1038/s41423-026-01464-1","url":null,"abstract":"Proteins containing the broad-complex, tramtrack and bric-à-brac (BTB) domain, also referred to as the poxvirus and zinc finger (POZ) domain, play a variety of cellular roles. As key mediators of protein–protein interactions, these proteins participate in the regulation of various biological processes. In this study, we discovered that ankyrin repeat and BTB domain-containing protein 1 (ABTB1) acts as an important regulator of the differentiation of T helper 17 (Th17) cells. ABTB1 deficiency promotes Th17 cell differentiation and exacerbates the symptoms associated with dextran sodium sulfate (DSS)-induced colitis by enhancing Th17 cell-mediated inflammatory responses. Furthermore, the loss of ABTB1 decreases the polyubiquitination of signal transducer and activator of transcription 3 (STAT3) while increasing both the total expression and phosphorylation levels of the STAT3 protein, which are critical for Th17 cell differentiation. On a mechanistic level, this study provides the first evidence that neddylated ABTB1 functions as a novel E3 ubiquitin ligase. Neddylated ABTB1 mediates the K27-, K33-, and K48-linked polyubiquitination of STAT3, thereby promoting its degradation via the ubiquitin–proteasome pathway. Accordingly, ABTB1 inhibits the excessive activation of STAT3 and ultimately suppresses Th17 cell differentiation. Overall, our research demonstrates the critical role of ABTB1 in regulating the differentiation and function of Th17 cells under conditions of autoimmune diseases. Thus, ABTB1 may represent a potential therapeutic target for inflammatory bowel disease (IBD) and other autoimmune disorders.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"23 10","pages":"1285-1307"},"PeriodicalIF":23.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}