| Project/Area Number |
26293256
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
川村 龍吉 山梨大学, 総合研究部, 准教授 (70262657)
柴垣 直孝 山梨大学, 総合研究部, 准教授 (40262662)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Keywords | 肥満細胞 / ヘルペスウイルス / アラーミン / IL-33 / herpes simplex virus / mast cell / innate immunity / HSV / HIV / ランゲルハンス細胞 / 抗菌ペプチド / Alarmin / マスト細胞 / ケラチノサイト |
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| Outline of Final Research Achievements |
Here, we found that, in herpes simplex virus (HSV)-2-infected murine skin, IL-33 protein kinetics paralleled the kinetics of HSV titer, suggesting that productive viral replication promotes IL-33 release in skin. Ex vivo mast cell (MC) activation analysis demonstrated that supernatants of HSV-2-infected epidermis of wild type (WT) mice, but not IL-33-/- mice, induced TNF-αproduction by bone marrow-derived MCs (BMMCs), indicating that IL-33 released from HSV-2-infected epidermis activates BMMCs. To see whether IL-33/ST2 signaling on MCs contributes to antiviral host defense, bone marrow-derived mast cells (BMMCs) generated from WT or ST2-/- mice were reconstituted in the skin of MCs deficient (W/Wv) mice before HSV-2 infection. We found that intradermal reconstitution with WT-BMMCs, but not ST2-/- BMMCs, significantly restored the clinical severity and mortality in HSV-2-infected W/Wv mice, indicating the importance of IL-33/ST2 axis on MCs in host defense.
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