Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 11, Pages 3228-3238Publisher
WILEY
DOI: 10.1002/eji.200838839
Keywords
Kinases; Knockout mice; Mast cells; Signal transduction
Categories
Funding
- START program [Y-163]
- Austrian Federal Ministry of Science and Research
- Austrian Research Fund (FWF) [F2305-B13]
- EU Marie Curie RTN
- Deutsche Forschungsgemeinschaft [Schm 2128/1-1]
- Austrian Science Fund (FWF) [W1212] Funding Source: Austrian Science Fund (FWF)
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Mast cells play crucial roles in a variety of normal and pathophysiological processes and their activation has to be tightly controlled. Here, we demonstrate that the protein tyrosine kinase Tec is a crucial regulator of murine mast cell function. Tee was activated upon Fc epsilon RI stimulation of BM-derived mast cells (BMMC). The release of histamine in the absence of Tec was normal in vitro and in vivo; however, leukotriene C-4 levels were reduced in Tec(-/-) BMMC. Furthermore, the production of IL-4 was severely impaired, and GM-CSF, TNF-alpha and IL-13 levels were also diminished. Finally, a comparison of WT, Tec(-/-), Btk(-/-) and Tec(-/-)Btk(-/-) BMMC revealed a negative role for Btk in the regulation of IL-4 production, while for the efficient production of TNF-alpha, IL-13 and GM-CSF, both Tee and Btk were required. Our results demonstrate a crucial role for Tee in mast cells, which is partially different to the function of the well-characterized family member Btk.
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