Interleukin-2-inducible T cell kinase regulates mast cell degranulation and acute allergic responses.
Bruton's tyrosine kinase (Btk) is thought to positively regulate mast cell activation, implying a role in allergic responses. We have compared acute and late phase allergic airway reactions in mice lacking either Btk or interleukin-2-inducible T cell kinase (Itk), another Tec kinase expressed in mast cells. Btk(-/-) mice showed minor protection against allergic symptoms when challenged with allergen via the airways. In sharp contrast, both acute and late phase inflammatory allergic responses were markedly reduced in Itk(-/-) mice. Notably, airway mast cell degranulation in Itk(-/-) mice was severely impaired, despite wild-type levels of allergen-specific IgE and IgG1. The degranulation defect was confirmed in DNP-conjugated human serum albumin-challenged mice passively sensitized with anti-DNP IgE antibodies, and was also observed after direct G-protein stimulation with the mast cell secretagogue c48/80. Moreover, late phase inflammatory changes, including eosinophilia, lymphocyte infiltration, and Th2 cytokine production in the lungs, was eliminated in Itk(-/-) mice. Collectively, our data suggest a critical role of Itk in airway mast cell degranulation in vivo that together with an impaired T cell response prevents the development of both acute and late phase inflammatory allergic reactions.[1]References
- Interleukin-2-inducible T cell kinase regulates mast cell degranulation and acute allergic responses. Forssell, J., Sideras, P., Eriksson, C., Malm-Erjefält, M., Rydell-Törmänen, K., Ericsson, P.O., Erjefält, J.S. Am. J. Respir. Cell Mol. Biol. (2005) [Pubmed]
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