The protein tyrosine kinase Tec regulates mast cell function.
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. Tec 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 Tec and Btk were required. Our results demonstrate a crucial role for Tec in mast cells, which is partially different to the function of the well-characterized family member Btk.
Schmidt
Uwe
U
Division of Immunobiology, Institute of Immunology, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Austria.
Abramova
Anastasia
A
Boucheron
Nicole
N
Eckelhart
Eva
E
Schebesta
Alexandra
A
Bilic
Ivan
I
Kneidinger
Michael
M
Unger
Bernd
B
Hammer
Martina
M
Sibilia
Maria
M
Valent
Peter
P
Ellmeier
Wilfried
W
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase