The recognition and signaling pathway of cysteine protease activity in innate immune cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591419
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Shinshu University
• Principal Investigator: HIDA Shigeaki 信州大学, 学術研究院医学系, 准教授 (10345762)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: シグナル伝達 / 好塩基球 / サイトカイン

Outline of Final Research Achievements

Basophils have recently been recognized as an initiator of type 2 immune responses producing interleukin-4 (IL-4) in response to various stimuli. The cysteine protease papain was shown to induce production of IL-4 and other molecules in murine basophils. Papain has been shown to not only trigger IL-4 production but also activate antigen presentation machinery by basophils, thereby initiating Th2 responses. However, the papain receptor and the signaling pathway for IL-4 production induced by the protease remained unclear. Here we show that basophils lacking FcRγ failed to produce IL-4 in response to papain. Retroviral reconstitution experiments showed that the FcRγ-ITAM-Syk signaling pathway was essential in papain-induced IL-4 production. In addition, papain specifically induced the expression of IFN-related genes in bone marrow-derived basophils. These observations indicated that other receptors as well as FcRγ-associated molecules could potentially recognize the protease papain.

Free Research Field

免疫学