coinhibitory molecules in autoimmune diseasescoinhibitory分子在自身免疫性疾病.pdfVIP

Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2012, Article ID 269756, 7 pages doi:10.1155/2012/269756 Review Article Coinhibitory Molecules in Autoimmune Diseases Norihiko Watanabe1 and Hiroshi Nakajima2 1 Center for Rheumatic Diseases, Saiseikai Narashino Hospital, Narashino 275-8580, Japan 2 Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba 260-8670, Japan Correspondence should be addressed to Hiroshi Nakajima, nakajimh@faculty.chiba-u.jp Received 9 July 2012; Accepted 21 August 2012 Academic Editor: Timothy B. Niewold Copyright © 2012 N. Watanabe and H. Nakajima. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Coinhibitory molecules such as CTLA-4, PD-1 and BTLA negatively regulate immune responses. Multiple studies indicate that the deficiency or mutation of coinhibitory molecules leads to the development of autoimmune diseases in mice and humans, indicating that the negative signals from coinhibitory molecules are crucial for the prevention of autoimmunity. In some conditions, the administration of decoy coinhibitory receptors (e.g., CTLA-4 Ig) or mAb against coinhibitory molecules suppresses the responses of self-reactive T cells in autoimmune diseases. Therefore, modulation of coinhibitory signals seems to be an attractive approach to induce tolerance in autoimmune diseases in humans where the disease-inducing self-antigens are not known. Particularly, administration of CTLA-4 Ig has shown great promise in animal models of autoimmune diseases and has been gain