Fan Tingting, Tai Chi, Sleiman Kiah C, Cutcliffe Madeline P, Kim Haram, Liu Ye, Li Jianying, Xin Gang, Grashel Mollyanna, Baert Laurie, Ekeocha Chinwe, Vergenes Paige, Lima Svetlana, Lo Wan-Lin, Lin Judith, Hanaoka Beatriz, Tankersley Trevor N, Wang Min, Zhang Xuan, Tsokos George C, Jarjour Wael, Longman Randy, Wu Hsin-Jung Joyce
Division of Rheumatology and Immunology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ, USA.
Nat Immunol. 2025 May;26(5):790-804. doi: 10.1038/s41590-025-02125-7. Epub 2025 Apr 30.
Much remains unknown regarding T follicular helper 17 (T17) cells commonly found in autoimmune patients. We previously showed that (and here ask why) egress of gut segmented filamentous bacteria (SFB)-induced T cells from Peyer's patches (PP) to systemic sites promotes arthritis. We found splenic T17 cells are gut derived. Functional analyses using fate-mapping mice revealed a c-Maf-dependent and SFB-induced T17-to-T cell reprogramming that dominantly occurs in PPs. Unlike conventional T cells, T17-derived T cells are highly migratory and atypically concentrated in the dark zone of germinal centers (GCs). Compared to conventional T cells, T17-derived T cells express higher levels of T-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 T17-derived T signatures exist in rheumatoid arthritis patients. Thus, gut T cell plasticity generates atypical, potent T cells promoting systemic autoimmunity.
关于自身免疫性疾病患者中常见的滤泡辅助性T细胞17（T17），仍有许多未知之处。我们之前发现（在此提出疑问），肠道分节丝状菌（SFB）诱导的T细胞从派尔集合淋巴结（PP）迁移至全身部位会引发关节炎。我们发现脾脏中的T17细胞源自肠道。利用命运图谱小鼠进行的功能分析揭示了一种依赖c-Maf且由SFB诱导的T17细胞向T细胞的重编程，这种重编程主要发生在PP中。与传统T细胞不同，T17衍生的T细胞具有高度迁移性，且非典型地集中在生发中心（GC）的暗区。与传统T细胞相比，T17衍生的T细胞表达更高水平的T相关功能分子，并且与B细胞的结合更稳固。功能获得和功能丧失研究证明了它们在促进GC B细胞和关节炎方面的主导作用。值得注意的是，类风湿性关节炎患者体内存在小鼠肠道T17衍生的T细胞特征。因此，肠道T细胞可塑性产生了促进全身性自身免疫的非典型强效T细胞。
