Combinatorial roles of nuclear receptors in inflammation and immunity

Abstract

REVIEW ARTICLE published: 12 March 2012 doi: 10.3389/fimmu.2012.00020 SOCS, inflammation, and autoimmunity AkihikoYoshimura1*, Mayu Suzuki 1, Ryota Sakaguchi 1,Toshikatsu Hanada1 and HideoYasukawa2 1 Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Tokyo, Japan 2 Division of Cardiovascular Medicine, Kurume University School of Medicine, Kurume, Japan Edited by: Anna Rubartelli, National Cancer Research Institute, Italy Reviewed by: Masaaki Murakami, Osaka University, Japan Seth Lucian Masters, Walter and Eliza Hall Institute, Australia Cristina Albanesi, Istituo Dermopatico dell’Immacolata-IRCCS, Italy *Correspondence: Akihiko Yoshimura, Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. e-mail: yoshimura@a6.keio.jp Cytokines play essential roles in innate and adaptive immunity. However, excess cytokines or dysregulation of cytokine signaling will cause a variety of diseases, including allergies, autoimmune diseases, inflammation, and cancer. Most cytokines utilize the so-called Janus kinase–signal transducers and activators of transcription pathway. This pathway is nega- tively regulated by various mechanisms including suppressors of cytokine signaling (SOCS) proteins. SOCS proteins bind to JAK or cytokine receptors, thereby suppressing further signaling events. Especially, suppressor of cytokine signaling-1 (SOCS1) and SOCS3 are strong inhibitors of JAKs, because these two contain kinase inhibitory region at the N- terminus. Studies using conditional knockout mice have shown that SOCS proteins are key physiological as well as pathological regulators of immune homeostasis. Recent stud- ies have also demonstrated that SOCS1 and SOCS3 are important regulators of helper T cell differentiation and functions. This review focuses on the roles of SOCS1 and SOCS3 in T cell mediated inflammatory diseases. Keywords: cytokine, signal transduction, immunity

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