M.D., Ph.D. Professor Yoshinaga Ito
We study an interplay between immune system and self-organs/tissues, with a particular focus on its physiological roles and the mechanisms of disease development when the interaction becomes aberrant. We place autoimmunity and cancer immunology from an integrated perspective: both of them are ‘destruction of self-derived components by immune system’. We strive to discover key molecular pathways shared by both autoimmune diseases and cancer in order to develop innovative treatment arms for these devastating diseases.
Research and Education
T cells are responsible for critical traits of immune system; specificity, diversity and immunological memory. Through these functions, T cells play key roles in many life-threatening diseases including autoimmune disorders and cancer. We have developed novel technologies that resulted in characterizing T cells and their target autoantigens that cause autoimmune arthritis. By employing genome-wide CRISPR screen, we are also comprehensively identifying novel molecular pathways that sensitize cancer cells refractory to T cell-based immunotherapy.
In cancer, T cells become hyporesponsive due to a chronic antigen stimulation. On the other hand, in autoimmune disorders, although T cells receive a persistent stimulation from antigens, T cells stay responsive and destruct normal self tissues. Why these similar environments cause opposite T cell functions? We investigate cellular/molecular programs that govern these opposite T cell states in order to activate/suppress T cell-mediated immune reactions in cancer and autoimmunity.
- Ito Y, Ashenberg O, Pyrdol J, Luoma AM, Rozenblatt-Rosen O, Hofree M, Christian E, Ferrari de Andrade L, Tay RE, Teyton L, Regev A, Dougan SK, Wucherpfennig KW.
Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity. J Exp Med. 2018 Oct 1;215(10):2617-2635. doi: 10.1084/jem.20180300. Epub 2018 Sep 5.
- Ito Y, Hashimoto M, Hirota K, Ohkura N, Morikawa H, Nishikawa H, Tanaka A, Furu M, Ito H, Fujii T, Nomura T, Yamazaki S, Morita A, Vignali DA, Kappler JW, Matsuda S, Mimori T, Sakaguchi N, Sakaguchi S.
Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease.
Science. 2014 Oct 17;346(6207):363-8. doi: 10.1126/science.1259077.
- Ito Y, Usui T, Kobayashi S, Iguchi-Hashimoto M, Ito H, Yoshitomi H, Nakamura T, Shimizu M, Kawabata D, Yukawa N, Hashimoto M, Sakaguchi N, Sakaguchi S, Yoshifuji H, Nojima T, Ohmura K, Fujii T, Mimori T.
Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis.
Arthritis Rheum. 2009 Aug;60(8):2294-303. doi: 10.1002/art.24687.
Yoshinaga Ito, M.D., Ph.D. Professor
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