The tec family kinase, IL-2-inducible t cell kinase, differentially controls mast cell responses

Archana S. Iyer, Avery August

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The Tec family tyrosine kinase, IL-2-inducible T cell kinase (Itk), is expressed in T cells and mast cells. Mice lacking Itk exhibit impaired Th2 cytokine secretion; however, they have increased circulating serum IgE, but exhibit few immunological symptoms of allergic airway responses. We have examined the role of Itk in mast cell function and FcεRI signaling. We report in this study that Itk null mice have reduced allergen/IgE-induced histamine release, as well as early airway hyperresponsiveness in vivo. This is due to the increased levels of IgE in the serum of these mice, because the transfer of Itk null bone marrow-derived cultured mast cells into mast cell-deficient W/Wv animals is able to fully rescue histamine release in the W/Wv mice. Further analysis of Itk null bone marrow-derived cultured mast cells in vitro revealed that whereas they have normal degranulation responses, they secrete elevated levels of cytokines, including IL-13 and TNF-α, particularly in response to unliganded IgE. Analysis of biochemical events downstream of the FceRI revealed little difference in overall tyrosine phosphorylation of specific substrates or calcium responses; however, these cells express elevated levels of NFAT, which was largely nuclear. Our results suggest that the reduced mast cell response in vivo in Itk null mice is due to elevated levels of IgE in these mice. Our results also suggest that Itk differentially modulates mast cell degranulation and cytokine production in part by regulating expression and activation of NFAT proteins in these cells.

Original languageEnglish (US)
Pages (from-to)7869-7877
Number of pages9
JournalJournal of Immunology
Volume180
Issue number12
DOIs
StatePublished - 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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