Aberrant T follicular helper cells generated by T17 cell plasticity in the gut promote extraintestinal autoimmunity.

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.