The role of Frizzled Receptor Signaling in allergic airway inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08798
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Chiba University
• Principal Investigator: Arifumi Iwata 千葉大学, 大学院医学研究院, 助教 (90436353)
• Co-Investigator(Kenkyū-buntansha): 須藤 明 千葉大学, 大学院医学研究院, 准教授 (50447306) ; 横田 雅也 千葉大学, 医学部附属病院, 特任助教 (70721950)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: アレルギー性疾患 / 気管支喘息 / 樹状細胞

Outline of Final Research Achievements

Recently, several reports have suggested that the Wnt/Fzd signaling pathway, known for its crucial roles in development and organ formation, can influence T cell differentiation. However, a consensus has not yet been reached on this matter. Therefore, the aim of this study was to investigate the roles of the canonical and non-canonical Wnt pathways, focusing on the Frizzled receptors, in Th2 cell differentiation and to develop methods for their control.
We demonstrated that CD4T cells lacking Frizzled receptors specifically expressed in Th2 cells exhibited impaired Th2 cell differentiation even in an in vivo asthma environment, thus highlighting the critical role of Frizzled receptor signaling in Th2 cell differentiation.

Free Research Field

臨床免疫

Academic Significance and Societal Importance of the Research Achievements

Th2細胞分化誘導機構については、IL-4を中心としたautocrineな経路が中心的な役割を果たすことはよく知られているが、生体内でTh2細胞の誘導機構はいまだ不明である。
本研究では、Wnt関連蛋白のTh2細胞特異的な受容体刺激により、WntシグナルがTh2細胞分化に深く関係することを明らかとなった。これまでのサイトカインによる免疫制御とは異なる観点からの治療戦略が生まれることから、従来の免疫抑制療法に抵抗性の難治性患者への新規治療に結び付く可能性がある。