The study of mechanism of epidermotropism and metastasis of mycosis fungoides by establishing mouse mycosis fungoides model

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860967
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: FUKUDA Keitaro 慶應義塾大学, 医学部, 特任助教 (60464848)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 菌状息肉症 / Pautrier微小膿瘍 / 表皮抗原認識 / C-MYC / INK4A/ARF

Outline of Final Research Achievements

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.

Free Research Field

皮膚科学