Exploration of diseases caused by MARCH dysregulation

• Project/Area Number: 18K19462
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Hyogo Medical University
• Principal Investigator: ishido satoshi 兵庫医科大学, 医学部, 教授 (10273781)
• Co-Investigator(Kenkyū-buntansha): 小椋 英樹 兵庫医科大学, 医学部, 講師 (20573174)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: ユビキチン化 / 主要組織適合遺伝子複合体 / アレルギー / MHC class II

Outline of Final Research Achievements

At present, although MHC class II, which is a critical molecule for regulation of acquired immunity, has been known to be regulated by MARCH E3 ubiquitin ligase, it has remained unrevealed which medical concerned diseases are caused by dysregulation of MARCH and MHC class II. Therefore, we have explored the diseases caused by dysregulation of MARCH or MHC class II through genetical manipulation in mice. With a series of genetically modified mice, we have identified several immune diseases which are indeed caused by dysregulation of MHC class II ubiquitination.

Academic Significance and Societal Importance of the Research Achievements

現在、多くの免疫学的異常による病気がありますが、未だ原因不明の病気が数多くあり、その原因探索が行われています。その中で、我々は免疫を調節する根幹の分子MARCHを見出しました。しかしながら、現在、MARCHの異常がどのような病気の原因になっているのか分かっていません。そこで、MARCH遺伝子を改変したマウスを用いて、疾患の探索を行いました。この結果から、免疫学的異常による疾患発症の原因にMHC class IIのユビキチン化異常があることを念頭に検査、治療を考えることができると考えます。