Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Department of Genetics, University of Georgia, Athens, GA, United States.
Front Immunol. 2020 Jan 24;10:3103. doi: 10.3389/fimmu.2019.03103. eCollection 2019.
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.
白细胞介素 2（IL-2）诱导的 T 细胞激酶（ITK）是一种非受体酪氨酸激酶，在 T 细胞谱系中高度表达，调节 T 细胞发育和功能的多个方面，主要通过其在 T 细胞受体下游的功能。ITK 信号通路在 感染引起的活动性肺结核中的肺反应中的作用尚不清楚。我们在这里表明，患有活动性肺结核的人肺组织中存在改变的 T 细胞受体/ITK 信号，而 缺乏会损害小鼠对 的早期保护作用，同时伴有肺中产生白细胞介素 17A 的 γδ T 细胞发育缺陷。这些发现对与免疫反应改变和调节宿主免疫控制 活性的分子信号相关的人类易感性具有重要意义。增强 ITK 信号通路可能是针对 感染的一种替代策略，特别是在具有高度毒力株的情况下，白细胞介素 17A 发挥着至关重要的保护作用。
