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

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.

• Authors: Feng He, Hailan Yao, Zonghui Xiao, Jisheng Han, Jizhen Zou, Zhewei Liu
• Journal: Molecular immunology (Mol Immunol) Vol. 59 Issue 1 Pg. 30-8 (May 2014) ISSN: 1872-9142 [Electronic] England
• PMID: 24462896 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Cytokines
• Protein-Tyrosine Kinases
• emt protein-tyrosine kinase

Topics

• Animals
• Blotting, Western
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cell Proliferation
• Cells, Cultured
• Coxsackievirus Infections (genetics, immunology, virology)
• Cytokines (immunology, metabolism)
• Enterovirus B, Human (immunology, physiology)
• Flow Cytometry
• Host-Pathogen Interactions (immunology)
• Humans
• Jurkat Cells
• Leukocytes, Mononuclear (immunology, metabolism)
• Lymphocyte Activation (genetics, immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Myocarditis (genetics, immunology, virology)
• Protein-Tyrosine Kinases (genetics, immunology, metabolism)
• RNA Interference (immunology)
• Spleen (cytology, immunology, metabolism)
• Survival Analysis
• T-Lymphocytes (immunology, metabolism)