Local microbleeding induces the accumulation of Th17 cells and the development of IL-17– and IL-6–dependent arthritis in the absence of cognate antigen recognition by CD4+ T cells

Aledort

Andersson

Atsumi

Awasthi

Bettelli

Bianchi

Chapuy-Regaud

Cherwinski

Compagno

Constant

Daisuke Kamimura

Elsaid

Falgarone

Feldmann

Glimcher

Gudmundsdottir

Hakobyan

Harrington

Hasler

Hideki Ogura

Hirano

Hirota

Imboden

Ishihara

Iwakura

Jang

Khiong

King

Kivity

Kiyoshi Takatsu

Larbi

Lenz

Maffia

Manco-Johnson

Marrack

Masaaki Murakami

Masaya Harada

Mathis

Matsumoto

Minegishi

Mineko Tsuruoka

Minoru Kanamoto

Mocci

Mosmann

Muromoto

Münz

Nakagawa

Nickdel

Nishihara

Nishimoto

Ogura

Ohtani

O’Shea

Park

Polgár

Rebouissou

Sakaguchi

Sawa

Shogo Asano

Sims

Skapenko

Steinman

Surh

Takeda

Takizawa

Tamura

Toshio Hirano

Uchiyama

Van Steendam

Veldhoen

Williams

Yasunobu Arima

Yoichiro Iwakura

Yoshida

Yukihisa Sawa

Yuko Okuyama

Zhang

English

PubMed

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.</jats:p

Crossref

The Journal of Experimental Medicine

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

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3023133

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

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