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.
Sahu
Nisebita
N
Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology & Infectious Disease, The Pennsylvania State University, University Park, PA 16802, USA. nsahu@partners.org
August
Avery
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase
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