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

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

Research output: Contribution to journalArticle

873 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Th17 Cells
Autoantibodies
Arthritis
Germinal Center
Bacteria
Mucous Membrane
Specific Pathogen-Free Organisms
Interleukin-17
Autoimmune Diseases
B-Lymphocytes
Cytokines
Serum
Population

Keywords

  • CELLIMMUNO
  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Wu, H-J. J., Ivanov, I. I., Darce, J., Hattori, K., Shima, T., Umesaki, Y., ... Mathis, D. (2010). Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity, 32(6), 815-827. https://doi.org/10.1016/j.immuni.2010.06.001

Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. / Wu, Hsin-Jung Joyce; Ivanov, Ivaylo I.; Darce, Jaime; Hattori, Kimie; Shima, Tatsuichiro; Umesaki, Yoshinori; Littman, Dan R.; Benoist, Christophe; Mathis, Diane.

In: Immunity, Vol. 32, No. 6, 06.2010, p. 815-827.

Research output: Contribution to journalArticle

Wu, H-JJ, Ivanov, II, Darce, J, Hattori, K, Shima, T, Umesaki, Y, Littman, DR, Benoist, C & Mathis, D 2010, 'Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells', Immunity, vol. 32, no. 6, pp. 815-827. https://doi.org/10.1016/j.immuni.2010.06.001
Wu, Hsin-Jung Joyce ; Ivanov, Ivaylo I. ; Darce, Jaime ; Hattori, Kimie ; Shima, Tatsuichiro ; Umesaki, Yoshinori ; Littman, Dan R. ; Benoist, Christophe ; Mathis, Diane. / Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. In: Immunity. 2010 ; Vol. 32, No. 6. pp. 815-827.
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