Sahu Nisebita, August Avery
Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology & Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA.
Curr Top Med Chem. 2009;9(8):690-703. doi: 10.2174/156802609789044443.
Interleukin-2-inducible T cell kinase (ITK) is a non-receptor tyrosine kinase expressed in T cells, NKT cells and mast cells which plays a crucial role in regulating the T cell receptor (TCR), CD28, CD2, chemokine receptor CXCR4, and FcepsilonR-mediated signaling pathways. In T cells, ITK is an important mediator for actin reorganization, activation of PLCgamma, mobilization of calcium, and activation of the NFAT transcription factor. ITK plays an important role in the secretion of IL-2, but more critically, also has a pivotal role in the secretion of Th2 cytokines, IL-4, IL-5 and IL-13. As such, ITK has been shown to regulate the development of effective Th2 response during allergic asthma as well as infections of parasitic worms. This ability of ITK to regulate Th2 responses, along with its pattern of expression, has led to the proposal that it would represent an excellent target for Th2-mediated inflammation. We discuss here the possibilities and pitfalls of targeting ITK for inflammatory disorders.
白细胞介素-2诱导型T细胞激酶（ITK）是一种在T细胞、自然杀伤T细胞（NKT细胞）和肥大细胞中表达的非受体酪氨酸激酶，在调节T细胞受体（TCR）、CD28、CD2、趋化因子受体CXCR4以及FcepsilonR介导的信号通路中发挥关键作用。在T细胞中，ITK是肌动蛋白重组、磷脂酶Cγ（PLCγ）激活、钙动员以及活化T细胞核因子（NFAT）转录因子的重要介质。ITK在白细胞介素-2（IL-2）的分泌中发挥重要作用，但更关键的是，它在辅助性T细胞2（Th2）细胞因子IL-4、IL-5和IL-13的分泌中也起着关键作用。因此，ITK已被证明在过敏性哮喘以及寄生虫感染期间调节有效的Th2反应的发展。ITK调节Th2反应的这种能力及其表达模式，使得人们提出它可能是Th2介导的炎症的一个理想靶点。我们在此讨论针对ITK治疗炎症性疾病的可能性和潜在问题。
