Interleukin-2-Inducible T-Cell Kinase Deficiency Impairs Early Pulmonary Protection Against Infection

Authors

Lu Huang, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Kaixiong Ye, Department of Genetics, University of Georgia, Athens, GA, United States.
Michael C. McGee, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.
Natalie F. Nidetz, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.
Jessica P. Elmore, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Candice B. Limper, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Teresa L. Southard, Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
David G. Russell, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Avery August, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Weishan Huang, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.

Document Type

Article

Publication Date

1-1-2019

Abstract

Interleukin-2 (IL-2) inducible T-cell kinase (ITK) is a non-receptor tyrosine kinase highly expressed in T-cell lineages and regulates multiple aspects of T-cell development and function, mainly through its function downstream of the T-cell receptor. deficiency can lead to CD4 lymphopenia and Epstein-Bar virus (EBV)-associated lymphoproliferation and recurrent pulmonary infections in humans. However, the role of the ITK signaling pathway in pulmonary responses in active tuberculosis due to infection is not known. We show here that human lungs with active tuberculosis exhibit altered T-cell receptor/ITK signaling and that deficiency impaired early protection against in mice, accompanied by defective development of IL-17A-producing γδ T cells in the lungs. These findings have important implications of human genetics associated with susceptibility to due to altered immune responses and molecular signals modulating host immunity that controls activity. Enhancing ITK signaling pathways may be an alternative strategy to target infection, especially in cases with highly virulent strains in which IL-17A plays an essential protective role.

Publication Source (Journal or Book title)

Frontiers in immunology

First Page

3103

Recommended Citation

Huang, L., Ye, K., McGee, M. C., Nidetz, N. F., Elmore, J. P., Limper, C. B., Southard, T. L., Russell, D. G., August, A., & Huang, W. (2019). Interleukin-2-Inducible T-Cell Kinase Deficiency Impairs Early Pulmonary Protection Against Infection. Frontiers in immunology, 10, 3103. https://doi.org/10.3389/fimmu.2019.03103