Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs

C. Pierce Bradley, Fei Teng, Krysta M. Felix, Teruyuki Sano, Debdut Naskar, Katharine E. Block, Haochu Huang, Kenneth S. Knox, Dan R. Littman, Hsin Jung Joyce Wu

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gut-lung crosstalk and dual TCR-based autoimmunity. Lung complications significantly contribute to rheumatoid arthritis (RA)-related mortality. Bradley et al. demonstrate that gut microbiota SFB trigger RA-related lung pathology during the pre-arthritic phase by inducing Th17 cells of the gut-lung axis. SFB selectively expand autoimmune, dual TCR-expressing Th17 cells that sense both SFB peptide and self-antigen.

Original languageEnglish (US)
Pages (from-to)697-704.e4
JournalCell Host and Microbe
Volume22
Issue number5
DOIs
StatePublished - Nov 8 2017

Keywords

  • Th17 cells
  • autoimmune
  • dual TCR
  • gut microbiota
  • gut-lung axis
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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