Immunity
Volume 44, Issue 4, 19 April 2016, Pages 875-888
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Article
Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer’s Patch T Follicular Helper Cells

https://doi.org/10.1016/j.immuni.2016.03.013Get rights and content
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Highlights

  • SFB enhance autoimmune arthritis, reflected by elevated auto-Ab, GC, and Tfh cell responses

  • SFB-driven differentiation and egress of PP Tfh cells to systemic sites cause disease

  • SFB induce PP Tfh cell differentiation by limiting the access of IL-2 to PP CD4+ T cells

  • DCs are required for SFB-mediated IL-2Rα suppression and Bcl-6 upregulation in PPs

Summary

Gut microbiota profoundly affect gut and systemic diseases, but the mechanism whereby microbiota affect systemic diseases is unclear. It is not known whether specific microbiota regulate T follicular helper (Tfh) cells, whose excessive responses can inflict antibody-mediated autoimmunity. Using the K/BxN autoimmune arthritis model, we demonstrated that Peyer’s patch (PP) Tfh cells were essential for gut commensal segmented filamentous bacteria (SFB)-induced systemic arthritis despite the production of auto-antibodies predominantly occurring in systemic lymphoid tissues, not PPs. We determined that SFB, by driving differentiation and egress of PP Tfh cells into systemic sites, boosted systemic Tfh cell and auto-antibody responses that exacerbated arthritis. SFB induced PP Tfh cell differentiation by limiting the access of interleukin 2 to CD4+ T cells, thereby enhancing Tfh cell master regulator Bcl-6 in a dendritic cell-dependent manner. These findings showed that gut microbiota remotely regulated a systemic disease by driving the induction and egress of gut Tfh cells.

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