Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 Cells

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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2010-06, Vol.32 (6), p.815-827
Main Authors: Wu, Hsin-Jung, Ivanov, Ivaylo I., Darce, Jaime, Hattori, Kimie, Shima, Tatsuichiro, Umesaki, Yoshinori, Littman, Dan R., Benoist, Christophe, Mathis, Diane
Format: Article
Language:English
Subjects:
Animal models
Animals
Arthritis
Arthritis, Experimental - immunology
Arthritis, Experimental - microbiology
Arthritis, Rheumatoid - immunology
Arthritis, Rheumatoid - microbiology
Autoimmune diseases
Bacteria
Bacteria - immunology
Cell Separation
CELLIMMUNO
Disease
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Gene expression
Immune system
Interleukin-17 - immunology
Intestines - microbiology
Lymphocytes
Mice
MICROBIO
MOLIMMUNO
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes, Helper-Inducer - immunology
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Summary: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. ► Commensal microbes drive arthritis development in the K/BxN mouse model ► Germ-free mice had deficits in gut and spleen Th17 cells and in serum autoantibodies ► IL-17 blockade could prevent arthritis through a direct effect on splenic B cells ► Segmented filamentous bacteria could alone trigger arthritis in germ-free K/BxN mice
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2010.06.001