ITK inhibitors in inflammation and immune-mediated disorders.

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.