Inhibition of IL-2 inducible T-cell kinase alleviates T-cell activation and murine myocardial inflammation associated with CVB3 infection |
| |
Authors: | Feng He Hailan Yao Zonghui Xiao Jisheng Han Jizhen Zou Zhewei Liu |
| |
Institution: | 1. Molecular Immunology Laboratory, Capital Institute of Pediatrics, Beijing 100020, China;2. Medical Department, Aerospace 731 Hospital, Beijing 100074, China;3. Pathology Laboratory, Capital Institute of Pediatrics, Beijing 100020, China |
| |
Abstract: | BackgroundCoxsackievirus B3 (CVB3) infection causes myocarditis, pancreatitis, and aseptic meningitis. Targeting antigen-specific T cell reactions might be a promising way to alleviate the inflammatory response induced by CVB3 infection. IL-2-inducible T-cell kinase (ITK), a member of Tec kinase family expressed mainly in T cells, plays an important role in the activation of T cells. The role of ITK in viral myocarditis induced by CVB3 has not been documented.MethodologyIn this study, we inhibited the ITK expression in Jurkat cells, primary human peripheral blood mononuclear cells (PBMC), and mouse splenocytes by ITK-specific siRNA. The inhibition efficiently suppressed cell proliferation (P < 0.05) and T-cell related cytokine secretion (P < 0.05). In order to inhibit ITK in vivo, the pGCSIL plasmid containing short hairpin RNAs targeting ITK was constructed and transduced into mice infected with CVB3. ITK-inhibited mice showed reduced cell proliferation (3, 5, and 7 days post-challenge, P < 0.05) as well as CD4+ and CD8+ T cells (5 days post-challenge, P < 0.05). The altered production of inflammatory cytokines alleviated pathologic heart damage and improved mice survival rate (P < 0.05).ConclusionITK played an important role in the T cell development and represented a new target for the modulation of T-cell-mediated inflammatory response by CVB3 infection. |
| |
Keywords: | ITK IL-2-inducible T-cell kinase CVB3 coxsackievirus B3 strain PBMC peripheral blood mononuclear cell RNAi RNA interference PFU plaque-forming units PHA phytohemagglutinin ConA concanavalin |
本文献已被 ScienceDirect 等数据库收录! |
|