Molecular mechanism of lysosome-dependent allergic inflammation

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K21654
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology; Immunology
• 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)
• Research Collaborator: OHSHIMA Daisuke ; TSUTSUI Hidemitsu ; DEMOTO Shiho ; SHIMIZU Yukiko ; OKAMURA Tadashi ; TANAKA Kaori (FURUYAMA Kaori) ; YOSHIDA Reiko (SUGITANI Reiko) ; KARIU Hitomi
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: リソソーム / マスト細胞 / アミノ酸トランスポーター / 炎症 / アレルギー

Outline of Final Research Achievements

Among various immune cells, mast cells or NK cells have the specialized intracellular compartments known as the histamine granules or cytotoxic granules. Our project aimed to reveal the molecular mechanism how the mast cell functions that are dependent on endosome/lysosome system, are regulated by SLC15A4, a lysosome-resident amino acid transporter. We found that SLC15A4-deficiency in mast cells led to the abnormality in the morphology of the lysosome/secretory granules and increased histamine synthesis or storage in the granules, which resulted in the increased histamine level upon degranulation both in vitro and in vivo. In SLC15A4-deficient cells, reduced mTORC activity augmented the activity of TFEB, the master transcription factor or the lysosome biogenesis, leading to the excess formation of secretory granules of mast cells. Our finding suggested that control of the lysosome condition by SLC15A4 is critical for the functional integrity of mast cells.

Free Research Field

分子免疫学