Understanding the mechanisms of IRF5-selective regulation towards the development of novel SLE treatment

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19161
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Yokohama City University
• Principal Investigator: Ban Tatsuma 横浜市立大学, 医学部, 助教 (50635357)
• Research Collaborator: TAMURA Tomohiko ; NISHIYAMA Akira ; SATO Go ; KIKUCHI Masako ; MANABE Akio
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 転写因子 / IRF5 / 自然免疫応答 / 全身性エリテマトーデス / MAPキナーゼ

Outline of Final Research Achievements

In this study, aiming to identify novel therapeutic targets for systemic lupus erythematosus (SLE), a refractory autoimmune disease, we analyzed the selective regulatory mechanism of the transcription factor IRF5, which is involved in the pathogenesis of SLE. As a result, it was suggested that transcription factors activated via the MAP kinase (MAPK) pathway are involved in selective control of IRF5 activity. Furthermore, inhibition of MAPK resulted in suppression of IRF5-dependent innate immune responses in mice. Clarifying the mechanism of IRF5 regulation by transcription factors activated via the MAPK pathway might lead to the development of therapy for SLE and other IRF5-related diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

これまで不明であったMAPキナーゼ経路による選択的なIRF5活性制御機構が存在することを明らかにした。IRF5はSLEのみならず、シェーグレン症候群や全身性強皮症など他の自己免疫疾患の病態発症とも関連するため、IRF5選択的制御機構の解明はこれらの疾患の治療法開発にも繋がると期待できる。