Background/Purpose: Much remains unknown regarding T follicular helper 17 (Tfh17) cells in autoimmunity. We previously showed, and here ask why, egress of gut segmented filamentous bacteria (SFB)-induced Tfh cells from Peyer’s patch (PP) promotes arthritis.

Methods: KikGR transgenic mouse line ubiquitously expresses the green (KikG)-to-red (KikR) photoconvertible fluorescent protein in its cells. We established a surgical procedure to track Peyer’s patch (PP) cell migration in KikGR.K/BxN mice. This was done by treating PPs with violet laser light, thereby photoconverting and marking PP cells, which allowed us to monitor the migration of these photoconverted PP cells to the spleen. We also performed scRNA seq analysis and ex vivo assays using samples from both mouse and rheumatoid arthritis patients to study T cell-B cell interactions.

Results: We found splenic Tfh17 cells are gut-derived. Functional and scRNA-seq trajectory analyses using fate-mapping mice revealed a c-Maf-dependent and SFB-induced Th17-to-Tfh cell reprogramming that dominantly occurs in PPs. Differences between conventional and T-cell plasticity-derived Tfh cells were previously unknown. We found, unlike conventional Tfh cells, Th17-derived Tfh cells are highly migratory and atypically concentrated in the dark zone (DZ) of germinal centers (GCs). They robustly conjugate with B cells displaying high somatic hypermutation and promote strong GC B cell responses. Both DZ-localization and potent B cell-helper function empower them to enhance arthritis. Murine, PP Th17-derived Tfh signatures exist in rheumatoid arthritis patients.

Conclusion: Our findings provide much needed knowledge on Tfh cells and indicate that gut-induced T cell plasticity mediates a cross-tissue communication via Th17^Der Tfh cells that advances autoimmunity outside the intestine.

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/aberrant-tfh-cells-generated-by-th17-cell-plasticity-in-the-gut-promote-autoimmune-arthritis/