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

• 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
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2010.06.001

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