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Interleukin-2–Inducible T Cell Kinase Regulates Mast Cell Degranulation and Acute Allergic Responses

2005; American Thoracic Society; Volume: 32; Issue: 6 Linguagem: Inglês

10.1165/rcmb.2004-0348oc

1535-4989

Johan Forssell, Paschalis Sideras, Christina Eriksson, Monika Malm-Erjefält, Kristina Rydell‐Törmänen, Per‐Olof Ericsson, Jonas S. Erjefält,

T-cell and B-cell Immunology

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.