本文采用的英格恩产品: RNA-Entranster-invivo
Inhibition of IL-2 inducible T-cell kinase alleviates T-cell activation and murine myocardial inflammation associated with CVB3 infection
Feng He 1 , Hailan Yao 1 , Zonghui Xiao 1 , Jisheng Han 2 , Jizhen Zou 3 , Zhewei Liu 4
Affiliations
- 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.
- 4 Molecular Immunology Laboratory, Capital Institute of Pediatrics, Beijing 100020, China. Electronic address: zheweiliu@163.com.
Abstract
Background: Coxsackievirus 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.
Methodology: In 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).
Conclusion: ITK 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: Coxsackievirus B3; ITK; Myocarditis; RNAi.