Tsuneyo Mimori, M.D., Ph.D. Professor
The Department of Rheumatology and Clinical Immunology is dealing with researches, education and clinical survice of diseases in which immunological abnormalities are involved in development and pathogenesis, including autoimmune diseases, connective tissue diseases, rheumatic diseases and allergic diseases. Besides, since the therapeutic application of immunology covers infection, transplantation and cancer therapy, clinical Immunology will become more important field in terms of its wide application. We aim to establish the base of clinical immunology and rheumatology in Japan, by elucidating the mechanisms of autoimmune diseases, developing the new diagnostic and therapeutic strategy, offering the advanced clinical service, and training the leading researchers and specialists in this field.
Research and Education
We are conducting the following studies to examine etiology and pathogenesis of systemic autoimmune diseases and to develop new diagnostic and therapeutic strategy for these diseases.
1) Clinical and pathogenic significance of autoantibodies: We discovered many autoantibodies in connective tissue/ rheumatic diseases, identified their target autoantigens, and elucidated their clinical and pathogenic significance. We are now developing the assay systems to detect those autoantibodies (Fig.1).
2) Disease-associated genes in rheumatic diseases: In multicenter genome-wide association study, MBP, AIRE and CCR6 were identified as new RA-related genes. Moreover, we demonstrated that autoantibody to MBP was present in RA patient sera and MBP was expressed in RA synovial tissues. We further investigate disease-related genes involving in severity of RA and other autoimmune diseases.
3) Pathogenic mechanisms of arthritis in rheumatic disease: We are investigating cytokines, immune cells and environmental factors involving in development of arthritides using arthritis model mice. We have demonstrated so far that IL-17 was produced from γδT cells but not Th17 cells in collagen-induced arthritis model, immune complex stimulated the production of IL-17 from granulocytes, and C5a played an important role in differentiation and activation of Th17 cells.
Fig. 1. Detection of autoantibodies in patients with connective tissue diseases by RNA- immunoprecipitation assay
Fig. 2. Expression of the MBP protein in synovial tissues of patients with rheumatoid arthritis
Recent Publications1. Mimori T, Nakashima R, Hosono Y: Interstitial lung disease in myositis: Clinical subsets, biomarkers, and treatment. Curr Rheumatol Rep 14(3):264-74, 2012.
2. Okada Y, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Kawaguchi T, Stahl EA, Kurreeman FA, Nishida N, Ohmiya H, Myouzen K, Takahashi M, Sawada T, Nishioka Y, Yukioka M, Matsubara T, Wakitani S, Teshima R, Tohma S, Takasugi K, Shimada K, Murasawa A, Honjo S, Matsuo K, Tanaka H, Tajima K, Suzuki T, Iwamoto T, Kawamura Y, Tanii H, Okazaki Y, Sasaki T, Gregersen PK, Padyukov L, Worthington J, Siminovitch KA, Lathrop M, Taniguchi A, Takahashi A, Tokunaga K, Kubo M, Nakamura Y, Kamatani N, Mimori T, Plenge RM, Yamanaka H, Momohara S, Yamada R, Matsuda F, Yamamoto K: Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. Nat Genet 44(5):511-6, 2012.
3. Terao C, Ohmura K, Katayama M, Takahashi M, Kokubo M, Diop G, Toda Y, Yamamoto N, Shinkura R, Shimizu M, Gut I, Heath S, Melchers I, Manabe T, Lathrop M, Mimori T, Yamada R, Matsuda F: Myelin basic protein as a novel genetic risk factor in rheumatoid arthritis – a genome-wide study combined with immunological analyses. PLoS One 6(6):e20457, 2011.
4. Nakashima R, Imura Y, Kobayashi S, Yukawa N, Yoshifuji H, Nojima T, Kawabata D, Ohmura K, Usui T, Fujii T, Okawa K, Mimori T: The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen recognized by anti-CADM-140 antibody. Rheumatology (Oxford) 49(3):433-440, 2010.
5. 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 60(8):2294-303, 2009.
Rheumatology and Clinical ImmunologyProfessor： Tsuneyo Mimori
Associate Professor： Takao Fujii
Senior Lecturer： Koichiro Ohmura
Assistant Professor ： Hajime Yoshifuji, Naoichiro Yukawa Yoshitaka Imura, Ran Nakashima