Establishment of murine model of autoimmune diseases

• Project/Area Number: 26670232
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Miyadera Hiroko 国立研究開発法人国立国際医療研究センター, その他部局等, その他 (40361464)
• Research Collaborator: Okamura Tadashi 国立研究開発法人国立国際医療研究センター, 研究所, 室長 (00333790) ; Nakano Kenta 国立研究開発法人国立国際医療研究センター, 研究所, 技術職員 ; Takanashi Rieko 国立研究開発法人国立国際医療研究センター, 研究所, 技術職員 ; Okabe Yuki 国立研究開発法人国立国際医療研究センター, その他部局等, 技術補佐員
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 主要組織適合性抗原 / 自己免疫疾患 / ヒト白血球抗原 / ヒト白血球抗原(HLA)

Outline of Final Research Achievements

Susceptibility to autoimmune diseases varies greatly among individuals. It has been known that various environmental and genetic factors contribute to susceptibility to autoimmune diseases. For certain autoimmune diseases, genes that encode human leukocyte antigens (HLA) is the strongest susceptibility loci, however, underlying mechanisms remain elusive. In this study, we have studied mechanism of autoimmune diseases by modifying the genes that encode major histocompatibility complex (MHC) of mouse, which is analogous to human HLA, to understand potential roles of HLA/MHC class II in the development of autoimmunity.

Research Products

• [Journal Article] Autoimmune susceptible HLA alleles encode unstable proteins. (2015)
  • Author(s): Miyadera, H., Ohashi, J., Lernmark, A., Kitamura, T., and Tokunaga, K.
  • Journal Title: J. Clin. Invest. Volume: 125 Issue: 1 Pages: 275-291
  • DOI: 10.1172/jci74961
  • Peer Reviewed / Open Access
• [Journal Article] Associations of human leukocyte antigens (HLA) with autoimmune diseases: Challenges in identifying the mechanism. (2015)
  • Author(s): Miyadera H*, Tokunaga K.
  • Journal Title: J Hum Genet Volume: 60 Issue: 11 Pages: 697-702
  • DOI: 10.1038/jhg.2015.100
  • Peer Reviewed
• [Journal Article] Independent strong association of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe mucosal involvement. (2014)
  • Author(s): Ueta M, Kaniwa N, Sotozono C, Tokunaga K, Saito Y, Sawai H, Miyadera H, Sugiyama E, Maekawa K, Nakamura R, Nagato M, Aihara M, Matsunaga K, Takahashi Y, Furuya H, Muramatsu M, Ikezawa Z, Kinoshita S.
  • Journal Title: Sci Rep. Volume: 4 Issue: 1 Pages: 4862-4862
  • DOI: 10.1038/srep04862
  • Peer Reviewed / Open Access
• [Presentation] HLAと自己免疫疾患の関連のメカニズム (2015)
  • Author(s): 宮寺 浩子
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-15
  • Invited