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

• ITK modulates T cell activation and proliferation in vitro.
• ITK expression can be inhibited by ITK-inhibiting plasmid injecting in mice.
• Inflammatory response by CVB3 infection can be ameliorated by inhibiting ITK expression in mice.

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.