Aberrant T follicular helper cells generated by TH17 cell plasticity in the gut promote extraintestinal autoimmunity. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • April 30, 2025

Research

keywords

  • Autoimmunity
  • Cell Plasticity
  • T Follicular Helper Cells
  • Th17 Cells

Identity

Digital Object Identifier (DOI)

  • 10.1038/s41590-025-02125-7

PubMed ID

  • 40307450

Additional Document Info

volume

  • 26

issue

  • 5