Innate immune receptors recognizing RNA as regulating ILC2 function related with pathogensis of asthma

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16165
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takashi Ishii 東京大学, 保健・健康推進本部, 助教 (30803118)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 気管支喘息 / 自然免疫 / RNA / ILC2

Outline of Final Research Achievements

In this study, we focused on MDA5 and RIG-I (RLRs), cytoplasmic RNA recognition receptors, whose expression in ILC2 has been suggested by existing databases. Our aim was to elucidate their functions, recognized ligands, and involvement in the pathogenesis of bronchial asthma using a mouse model, as well as to assess their potential as drug candidates. The results indicated that MDA5 plays a protective role in a house dust mite-induced bronchial asthma model. Additionally, it was suggested that MDA5 contributes to the difference in response activity to ligands potentially derived from in vivo reactivity with IL-33 in ILC2. We will continue to investigate the protective mechanisms of RLRs in bronchial asthma and the roles of exogenous/endogenous nucleic acids in ILC2.

Free Research Field

呼吸器疾患、免疫/炎症

Academic Significance and Societal Importance of the Research Achievements

本研究では気管支喘息の病態における自然免疫受容体のMDA5やRIG-I(RLRs)に焦点を当て、気管支喘息病態への関与をマウス生体モデルを用いて解明する事、特に気管支喘息病態に重要な細胞集団の一つである２型自然リンパ球(ILC2)に着目してRLRsの役割を検証した。
結果としてはMDA5がマウスの発気管支喘息モデルにおいて保護的な役割を持つこと、またILC2においてもMDA5による制御が示唆された。今後特にMDA5の気管支喘息における保護的機序の解明やILC2における詳細な役割を検討する事で、気管支喘息の新規治療候補の土台の一つとなりうる意義がある。