Clarification of peripheral tolerance mechanism involved in the onset of autoimmune skin diseases

2016 Fiscal Year Final Research Report

• Project/Area Number: 26253065
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: Amagai Masayuki 慶應義塾大学, 医学部(信濃町), 教授 (90212563)
• Co-Investigator(Kenkyū-buntansha): 高橋 勇人 慶應義塾大学, 医学部, 講師 (40398615) ; 山上 淳 慶應義塾大学, 医学部, 講師 (80327618)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Hayato 慶應義塾大学, 医学部, 専任講師 (40398615)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 自己免疫 / 免疫寛容 / 天疱瘡 / マウスモデル / デスモグレイン

Outline of Final Research Achievements

Utilizing desmoglein3 (Dsg3)-specific T cells (H1 T cells), two experimental models were established for clarification and analysis of peripheral immune tolerance mechanism. In the first model, we made mice, which lack Dsg3 only in the thymus by applying thymus transplantation into Nude mice, and then performed bone marrow transplantation to these mice from H1-tg mice. In these mice, H1 T cells matured in Dsg3 deficient thymus, and then, disappeared in Dsg3 expressing periphery. In the other model, H1 T cells existing in the periphery of H1-Dsg3-/- mice were adoptively transferred into WT mice. In these WT mice, H1 T cells disappeared after proliferation. Taking advantage of these models, we clarified that peripheral immune tolerance mechanism is initiated by antigen presentation to H1 T cells in skin-draining lymph node, and divided into proliferation phase and disappearance phase, orchestrated by some kinds of cell populations.

Free Research Field

皮膚科学