Scholarlink

<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>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Aberrant T follicular helper cells generated by TH17 cell plasticity in the gut promote extraintestinal autoimmunity

  • 期刊论文

  • 发表日期：

    2025年4月30日

查看全文
  • 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

摘要

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.