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Arthritis Research Therapy June 2005 Vol 7 No 3 Yoshimura et al. Review Negative regulation of cytokine signaling and immune responses by SOCS proteins Akihiko Yoshimura, Hitomi Nishinakamura, Yumiko Matsumura and Toshikatsu Hanada Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan Corresponding author: Akihiko Yoshimura, yakihiko@bioreg.kyushu-u.ac.jp Published: 30 March 2005 Arthritis Research Therapy 2005, 7:100-110 (DOI 10.1186/ar1741) This article is online at /content/7/3/100 © 2005 BioMed Central Ltd Abstract IL-2, IL-7, erythropoietin and growth hormones. These are Immune and inflammatory systems are controlled by multiple summarized in Fig. 1. cytokines, including interleukins and interferons. Many of these cytokines exert their biological functions through JAKs (Janus It has been recognized that sustained and/or excessive action tyrosine kinases) and STAT (signal transduction and activators of of cytokines can be harmful to organisms. Accordingly, transcription) transcription factors. CIS (cytokine-inducible SH2 several mechanisms have been reported to modulate (Src homology 2) protein) and SOCS (suppressor of cytokine cytokine signaling to prevent this overaction of cytokines. For signaling) are a family of intracellular proteins, several of which have emerged as key physiological regulators of cytokine-