Roles for TNFR superfamily molecules in regulation of ILC function

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15508
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Tohoku University
• Principal Investigator: ISHII Naoto 東北大学, 医学系研究科, 教授 (60291267)
• Co-Investigator(Kenkyū-buntansha): 宗 孝紀 富山大学, 大学院医学薬学研究部(薬学), 教授 (60294964)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 自然リンパ球 / サイトカイン / 補助刺激シグナル

Outline of Final Research Achievements

Group 2 innate lymphoid cells (ILC2) in the lung are activated by inhaled allergens and epithelial cytokine interleukin 33 (IL-33). We found that IL-33 alone was not sufficient to induce optimal ILC2 activation and that additional signals from glucocorticoid-induced TNFR-related protein (GITR) were essential. Gitr -/- mice displayed reduced numbers of ILC2 after administration of papain or IL-33, which resulted in impaired expression of IL-5 and IL-13 and diminished eosinophilia in the lung. Crosslinking of GITR with IL-33 synergistically activated NF-κB, p38, and Erk to induce IL-9 production, and autocrine IL-9 promoted IL-5 and IL-13 via STAT5. Accordingly, STAT5 activators, IL-2 and IL-9, restored the defective responses of Gitr -/- ILC2. Our results identify a previously unknown critical role for GITR co-signaling in initiating and promoting early ILC2 activation in the lung.

Free Research Field

免疫学