菌状息肉症(MF)は表皮向性を示し, interface dermatitis(ID)やPautrier微小膿瘍(PM)を認める。本研究はMFマウスの作製, MFの表皮浸潤機構の解明を目的に実施した。我々はデスモグレイン3を認識するTCR(H1), MFのInk4a/Arf(がん抑制遺伝子)変異, c-Myc(がん遺伝子)をCD4+T細胞に導入, Rag2欠損マウスに移植し, ID, PMをきたすMFマウスの作製に成功した。Ink4a/Arf変異・H1導入CD4+細胞はPMを形成せず, Ink4a/Arf変異・c-Myc導入CD4+T細胞はPMを形成した。PMの形成にはc-Mycが必要であることが示唆された。
Mycosis fungoides (MF) is a cutaneous T cell lymphoma of CD4+ T cells that show epidermotropism. It is characterized by interface dermatitis (ID) and Pautrier's microabscess (PM), a clustering of MF cells in the epidermis. This project was conducted to establish MF model mouse that recapitulate histopathology of MF and to clarify the mechanism of the development of PM. Since mutation in INK4A/ARF (tumor suppressor gene) and overexpression of C-MYC (oncogene) are associated in human MF, we isolated CD4+T cells from Ink4/Arf-/- mice and retrovirally transduced c-Myc and desmoglein 3 specific TCR (H1) that induces ID. T cells were then adoptively transferred into Rag2-/- mice, which lead to the development of ID and PM that recapitulated MF. In addition, transfer of Ink4/Arf-/- CD4+T cells transduced with c-Myc developed PM whereas transfer of Ink4/Arf-/- CD4+T cells transduced with H1 did not develop PM. Our results suggest that oncogene c-Myc is essential for the development of PM.

研究種目 : 若手研究(B)
研究期間 : 2013～2014
課題番号 : 25860967
研究分野 : 皮膚科学