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Interleukin-2-inducible T cell kinase regulates mast cell degranulation and acute allergic responses

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Author

Summary, in English

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 IgG(1). 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 Th-2 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.

Publishing year

2005

Language

English

Pages

511-520

Publication/Series

American Journal of Respiratory Cell and Molecular Biology

Volume

32

Issue

6

Document type

Journal article

Publisher

American Thoracic Society

Topic

  • Cell and Molecular Biology

Keywords

  • allergy and immunology
  • asthma
  • signal transduction

Status

Published

Research group

  • Airway Inflammation and Immunology

ISBN/ISSN/Other

  • ISSN: 1535-4989