| Project/Area Number |
16K15508
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Tohoku University |
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Principal Investigator |
ISHII Naoto 東北大学, 医学系研究科, 教授 (60291267)
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| 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)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 自然リンパ球 / サイトカイン / 補助刺激シグナル / アレルギー / GITR / 炎症 / 免疫学 |
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| 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.
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