The alarmin IL-33 derived from HSV-2-infected keratinocytes triggers mast cell-mediated antiviral innate immunity

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293256
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: University of Yamanashi
• Principal Investigator: SHIMADA Shinji 山梨大学, その他部局等, 学長 (10114505)
• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肥満細胞 / ヘルペスウイルス / アラーミン / IL-33

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.

Free Research Field

皮膚免疫