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

Am J Respir Cell Mol Biol. 2005 Jun;32(6):511-20. doi: 10.1165/rcmb.2004-0348OC. Epub 2005 Mar 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Asthma / immunology
  • Asthma / metabolism
  • Cell Degranulation / immunology*
  • Hypersensitivity / immunology*
  • Hypersensitivity / metabolism*
  • Mast Cells / enzymology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / immunology

Substances

  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Btk protein, mouse
  • emt protein-tyrosine kinase