title: Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells.
abstract: Cognate antigen recognition by CD4(+) T cells is thought to contribute to the tissue specificity of various autoimmune diseases, particularly those associated with class II MHC alleles. However, we show that localized class II MHC-dependent arthritis in F759 mice depends on local events that result in the accumulation of activated CD4(+) T cells in the absence of cognate antigen recognition. In this model, transfer of in vitro polarized Th17 cells combined with the induction of experimental microbleeding resulted in CCL20 production, the accumulation of T cells in the joints, and local production of IL-6. Disease induction required IL-17A production by transferred T cells, IL-6 and CCL20 expression, and STAT3 signaling in type I collagen-expressing cells. Our data suggest a model in which the development of autoimmune disease in F759 mice depends on four events: CD4(+) T cell activation regardless of antigen specificity, local events that induce T cell accumulation, enhanced sensitivity to T cell-derived cytokines in the tissue, and activation of IL-6 signaling in the tissue. This model provides a possible explanation for why tissue-specific antigens recognized by activated CD4(+) T cells have not been identified in many autoimmune diseases, especially those associated with class II MHC molecules.
authors.affiliation: Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okuyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Ogura
authors.forename: Shogo
authors.initials: S
authors.lastname: Asano
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Arima
authors.forename: Mineko
authors.initials: M
authors.lastname: Tsuruoka
authors.forename: Masaya
authors.initials: M
authors.lastname: Harada
authors.forename: Minoru
authors.initials: M
authors.lastname: Kanamoto
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Sawa
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamimura
authors.forename: Toshio
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001168:Arthritis / Q000276:immunology* / Q000378:metabolism; D006470:Hemorrhage / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000941:Antigens; D020381:Interleukin-17; D015850:Interleukin-6