Interface dermatitis(ID)は扁平苔蘚, 重症薬疹, GVHDや腫瘍随伴性天疱瘡など様々な皮膚疾患で共通して認められる病理組織像であるが, その分子メカニズムの詳細は不明である。本研究では遺伝子改変マウスを駆使してIDのメカニズムを解析し, その結果T細胞の転写因子であるT-bet, Stat1が重要であることを明らかにした。一方, 新しい免疫学的な概念の創出を目指し, IL-27下流で特異的に働く遺伝子を抽出したところ, コレステロール代謝酵素が同定でき, その働きが免疫制御に寄与することを明らかにした。本研究成果は皮膚炎における将来の新しい治療法の開発に大きく役立つことが期待できる。
Interface dermatitis is a pathological feature which is commonly observed in a variety of skin diseases including lichen plans, severe drug adverse reaction, graft-versus-host disease, paraneoplastic pemphigus and so on. The molecular mechanism that leads to interface dermatitis has not been understood. In this project, we took advantage of genetically engineered mice and discovered that T-bet and Stat1, crucial transcriptional factors in T cell differentiation, are keys in development of interface dermatitis. On the other hand, we also sought to establish a novel concept in the field of Immunology in this project. Through investigating genes which are specifically induced by interleukin (IL)-27, we found that cholesterol metabolizing enzyme is induced by IL-27 and the function contributes to immune regulation. Our results are promisingly expected to be useful to invent a new treatment for skin inflammatory diseases in the future.
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