Role of lysosome-resident amino acid transporters in inflammatory response

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07056
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: KOBAYASHI Toshihiko 国立研究開発法人国立国際医療研究センター, その他部局等, 副プロジェクト長 (40613203)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 炎症 / リソソーム / トランスポーター

Outline of Final Research Achievements

This research project was conducted to reveal the novel inflammatory signaling via a lysosome-resident amino acid transporter SLC15A3 and the molecular mechanism how this transporter contributes to the pathology of chronic inflammation. Throughout the period, we analyzed (1) the regulation mechanism of inflammation by SLC15A3, (2) identified the cell types that are positive for SLC15A3 during the inflammatory responses (3) searched the SLC15A3-associated molecules in order to understand the molecular machinery of SLC15A3-mediated inflammatory responses. As a result, we found out that SLC15A3 plays an important role in maintaining the pulmonary inflammation and symptom of diffuse alveolar hemorrhage, which was mostly mediated by inflammatory monocytes or neutrophils that express SLC15A3 gene at high level. We also identified several SLC15A3-associated molecules by research collaboration, and predicted the SLC15A3-mediated signaling pathways.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、リソソーム局在アミノ酸トランスポーターSLC15A3を介した新規炎症シグナルの制御機構、および慢性炎症疾患の病態制御における役割の解明を通じて、SLC15A3による新規炎症制御機構を明らかにすることを試みた。本研究成果の一部は既に学会等において公表済みであり、アミノ酸トランスポーターによる細胞内代謝変化を介した免疫応答の制御機構は、免疫学のみならず細胞生物学領域にも大きなインパクトと波及効果をもたらすことが期待される。