Inhibition of IL-2 inducible T-cell kinase alleviates T-cell activation and murine myocardial inflammation associated with CVB3 infection

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• 作者：Feng He^a ; Hailan Yao^a ; Zonghui Xiao^a ; Jisheng Han^b ; Jizhen Zou^c ; Zhewei Liu^a ; ^{zheweiliu@163.com" class="auth_mail}
• 关键词：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
• 刊名：Molecular Immunology
• 出版年：May, 2014
• 年：2014
• 卷：59
• 期：1
• 页码：30-38
• 全文大小：2883 K

文摘

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.