Format

Send to

Choose Destination
Immunity. 2016 Apr 19;44(4):875-88. doi: 10.1016/j.immuni.2016.03.013.

Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer's Patch T Follicular Helper Cells.

Author information

1
Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
2
Yakult Central Institute, Izumi 5-11, Kunitachi, Tokyo, Japan.
3
Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA; Arizona Arthritis Center, College of Medicine, University of Arizona, Tucson, AZ 85719, USA. Electronic address: joycewu@email.arizona.edu.

Abstract

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.

PMID:
27096318
PMCID:
PMC5296410
DOI:
10.1016/j.immuni.2016.03.013
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center