Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells

Hsin Jung Wu, Ivaylo I. Ivanov, Jaime Darce, Kimie Hattori, Tatsuichiro Shima, Yoshinori Umesaki, Dan R. Littman, Christophe Benoist, Diane Mathis

Research output: Contribution to journalArticlepeer-review

981 Scopus citations

Abstract

Commensal microbes can have a substantial impact on autoimmune disorders, but the underlying molecular and cellular mechanisms remain largely unexplored. We report that autoimmune arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, accompanied by reductions in serum autoantibody titers, splenic autoantibody-secreting cells, germinal centers, and the splenic T helper 17 (Th17) cell population. Neutralization of interleukin-17 prevented arthritis development in specific-pathogen-free K/BxN mice resulting from a direct effect of this cytokine on B cells to inhibit germinal center formation. The systemic deficiencies of the GF animals reflected a loss of Th17 cells from the small intestinal lamina propria. Introduction of a single gut-residing species, segmented filamentous bacteria, into GF animals reinstated the lamina propria Th17 cell compartment and production of autoantibodies, and arthritis rapidly ensued. Thus, a single commensal microbe, via its ability to promote a specific Th cell subset, can drive an autoimmune disease.

Original languageEnglish (US)
Pages (from-to)815-827
Number of pages13
JournalImmunity
Volume32
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • CELLIMMUNO
  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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