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PMID: 20620945 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Immunity ·Vol. 32 ·No. 6 ·2010-06-25 ·Pages 815-27

Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C, Mathis D

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.

MeSH Terms
Animals Arthritis, Experimental/immunology,microbiology Arthritis, Rheumatoid/immunology,microbiology Bacteria/immunology Cell Separation Enzyme-Linked Immunosorbent Assay Flow Cytometry Interleukin-17/immunology Intestines/microbiology Mice Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Helper-Inducer/immunology
Chemicals
Interleukin-17
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Wu Hsin-Jung
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Ivanov Ivaylo I
Darce Jaime
Hattori Kimie
Shima Tatsuichiro
Umesaki Yoshinori
Littman Dan R
Benoist Christophe
Mathis Diane
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2010.06.001
Published
2010-06-25
Pages
815-27
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2904693
Subset
IM
Grants
NIAID NIH HHS · T32 AI007386 · United States
NCI NIH HHS · T32 CA007386 · United States
NIAID NIH HHS · RC1 AI087266 · United States
NIAID NIH HHS · RC1AI 087266 · United States
NIAID NIH HHS · P01 AI065858 · United States
NIAID NIH HHS · P01 AI065858-040001 · United States
NIDDK NIH HHS · K99 DK085329 · United States
NIDDK NIH HHS · 1K99DK085329-01 · United States
Databases
GEO
GSE22140
Corrections
CommentIn
PMID: 21395373
External Links
PubMed source DOI: 10.1016/j.immuni.2010.06.001 PMC Full Text View journal details
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