Tingting Fan, Chi Tai, Kiah C. Sleiman, Madeline P. Cutcliffe, Haram Kim, Ye Liu, Jianying Li, Gang Xin, Mollyanna Grashel, Laurie Baert, Chinwe Ekeocha, Paige Vergenes, Svetlana Lima, Wan-Lin Lo, Judith Lin, Beatriz Hanaoka, Trevor N. Tankersley, Min Wang, Xuan Zhang, George C. Tsokos, Wael Jarjour, Randy Longman, Hsin-Jung Joyce Wu
{"title":"肠道内TH17细胞可塑性产生的异常T滤泡辅助细胞促进肠外自身免疫","authors":"Tingting Fan, Chi Tai, Kiah C. Sleiman, Madeline P. Cutcliffe, Haram Kim, Ye Liu, Jianying Li, Gang Xin, Mollyanna Grashel, Laurie Baert, Chinwe Ekeocha, Paige Vergenes, Svetlana Lima, Wan-Lin Lo, Judith Lin, Beatriz Hanaoka, Trevor N. Tankersley, Min Wang, Xuan Zhang, George C. Tsokos, Wael Jarjour, Randy Longman, Hsin-Jung Joyce Wu","doi":"10.1038/s41590-025-02125-7","DOIUrl":null,"url":null,"abstract":"<p>Much remains unknown regarding T follicular helper 17 (T<sub>FH</sub>17) cells commonly found in autoimmune patients. We previously showed that (and here ask why) egress of gut segmented filamentous bacteria (SFB)-induced T<sub>FH</sub> cells from Peyer’s patches (PP) to systemic sites promotes arthritis. We found splenic T<sub>FH</sub>17 cells are gut derived. Functional analyses using fate-mapping mice revealed a c-Maf-dependent and SFB-induced T<sub>H</sub>17-to-T<sub>FH</sub> cell reprogramming that dominantly occurs in PPs. Unlike conventional T<sub>FH</sub> cells, T<sub>H</sub>17-derived T<sub>FH</sub> cells are highly migratory and atypically concentrated in the dark zone of germinal centers (GCs). Compared to conventional T<sub>FH</sub> cells, T<sub>H</sub>17-derived T<sub>FH</sub> cells express higher levels of T<sub>FH</sub>-associated functional molecules and more robustly conjugate with B cells. Gain- and loss-of-function studies demonstrated their dominance in promoting GC B cells and arthritis. Notably, murine gut T<sub>H</sub>17-derived T<sub>FH</sub> signatures exist in rheumatoid arthritis patients. Thus, gut T cell plasticity generates atypical, potent T<sub>FH</sub> cells promoting systemic autoimmunity.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"24 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Aberrant T follicular helper cells generated by TH17 cell plasticity in the gut promote extraintestinal autoimmunity\",\"authors\":\"Tingting Fan, Chi Tai, Kiah C. Sleiman, Madeline P. Cutcliffe, Haram Kim, Ye Liu, Jianying Li, Gang Xin, Mollyanna Grashel, Laurie Baert, Chinwe Ekeocha, Paige Vergenes, Svetlana Lima, Wan-Lin Lo, Judith Lin, Beatriz Hanaoka, Trevor N. Tankersley, Min Wang, Xuan Zhang, George C. Tsokos, Wael Jarjour, Randy Longman, Hsin-Jung Joyce Wu\",\"doi\":\"10.1038/s41590-025-02125-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Much remains unknown regarding T follicular helper 17 (T<sub>FH</sub>17) cells commonly found in autoimmune patients. We previously showed that (and here ask why) egress of gut segmented filamentous bacteria (SFB)-induced T<sub>FH</sub> cells from Peyer’s patches (PP) to systemic sites promotes arthritis. We found splenic T<sub>FH</sub>17 cells are gut derived. Functional analyses using fate-mapping mice revealed a c-Maf-dependent and SFB-induced T<sub>H</sub>17-to-T<sub>FH</sub> cell reprogramming that dominantly occurs in PPs. Unlike conventional T<sub>FH</sub> cells, T<sub>H</sub>17-derived T<sub>FH</sub> cells are highly migratory and atypically concentrated in the dark zone of germinal centers (GCs). Compared to conventional T<sub>FH</sub> cells, T<sub>H</sub>17-derived T<sub>FH</sub> cells express higher levels of T<sub>FH</sub>-associated functional molecules and more robustly conjugate with B cells. Gain- and loss-of-function studies demonstrated their dominance in promoting GC B cells and arthritis. Notably, murine gut T<sub>H</sub>17-derived T<sub>FH</sub> signatures exist in rheumatoid arthritis patients. Thus, gut T cell plasticity generates atypical, potent T<sub>FH</sub> cells promoting systemic autoimmunity.</p>\",\"PeriodicalId\":19032,\"journal\":{\"name\":\"Nature Immunology\",\"volume\":\"24 1\",\"pages\":\"\"},\"PeriodicalIF\":27.7000,\"publicationDate\":\"2025-04-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41590-025-02125-7\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41590-025-02125-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Aberrant T follicular helper cells generated by TH17 cell plasticity in the gut promote extraintestinal autoimmunity
Much remains unknown regarding T follicular helper 17 (TFH17) cells commonly found in autoimmune patients. We previously showed that (and here ask why) egress of gut segmented filamentous bacteria (SFB)-induced TFH cells from Peyer’s patches (PP) to systemic sites promotes arthritis. We found splenic TFH17 cells are gut derived. Functional analyses using fate-mapping mice revealed a c-Maf-dependent and SFB-induced TH17-to-TFH cell reprogramming that dominantly occurs in PPs. Unlike conventional TFH cells, TH17-derived TFH cells are highly migratory and atypically concentrated in the dark zone of germinal centers (GCs). Compared to conventional TFH cells, TH17-derived TFH cells express higher levels of TFH-associated functional molecules and more robustly conjugate with B cells. Gain- and loss-of-function studies demonstrated their dominance in promoting GC B cells and arthritis. Notably, murine gut TH17-derived TFH signatures exist in rheumatoid arthritis patients. Thus, gut T cell plasticity generates atypical, potent TFH cells promoting systemic autoimmunity.
期刊介绍：
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
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