Published ahead of print on March 18, 2005, doi:10.1165/rcmb.2004-0348OC
© 2005 American Thoracic Society DOI: 10.1165/rcmb.2004-0348OC Interleukin-2–Inducible T Cell Kinase Regulates Mast Cell Degranulation and Acute Allergic ResponsesTransplantation Center, Foundation for Biomedical Research Academy of Athens, Athens, Greece; Institute for Medical Biosciences, Umeå University, Umeå; AstraZeneca R&D; Department of Clinical and Experimental Pharmacology, and Department of Experimental Medical Science, Lund University, Lund, Sweden Correspondence and requests for reprints should be addressed to Jonas Erjefält, Assoc Prof., Department of Experimental Medical Science, Airway Inflammation & Immunology Unit, BMC F10, Lund University Hospital, 221 84, Lund, Sweden. E-mail: jonas.erjefalt{at}mphy.lu.se 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.
Key Words: allergy and immunology • asthma • signal transduction This article has been cited by other articles:
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