| First Author | Forssell J | Year | 2005 |
| Journal | Am J Respir Cell Mol Biol | Volume | 32 |
| Issue | 6 | Pages | 511-20 |
| PubMed ID | 15778496 | Mgi Jnum | J:110944 |
| Mgi Id | MGI:3652437 | Doi | 10.1165/rcmb.2004-0348OC |
| Citation | Forssell J, et al. (2005) Interleukin-2-inducible T cell kinase regulates mast cell degranulation and acute allergic responses. Am J Respir Cell Mol Biol 32(6):511-20 |
| abstractText | 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. |
