Local microbleeding facilitates IL-6-and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells

Masaaki Murakami, Yuko Okuyama, Hideki Ogura, Shogo Asano, Yasunobu Arima, Mineko Tsuruoka, Masaya Harada, Minoru Kanamoto, Yukihisa Sawa, Yoichiro Iwakura, Kiyoshi Takatsu, Daisuke Kamimura, Toshio Hirano

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73 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)103-114
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number1
DOIs
Publication statusPublished - 2011 Jan 17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Murakami, M., Okuyama, Y., Ogura, H., Asano, S., Arima, Y., Tsuruoka, M., Harada, M., Kanamoto, M., Sawa, Y., Iwakura, Y., Takatsu, K., Kamimura, D., & Hirano, T. (2011). Local microbleeding facilitates IL-6-and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells. Journal of Experimental Medicine, 208(1), 103-114. https://doi.org/10.1084/jem.20100900