In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 28 ( 2005-07-12), p. 9866-9871
Kurzfassung:
Asthma is a disease of chronic airway inflammation in which T helper (Th) 2 cells play a critical role. The molecular mechanisms controlling Th2 differentiation and function are of paramount importance in biology and immunology. PKCζ has been implicated in the regulation of apoptosis and NF-κB, as well as in the control of T-dependent responses, although no defects were detected in naïve T cells from PKCζ –/– mice. Here, we report that PKCζ is critical for IL-4 signaling and Th2 differentiation. Thus, PKCζ levels are increased during Th2 differentiation, but not Th1 differentiation, of CD4 + T cells, and the loss of PKCζ impairs the secretion of Th2 cytokines in vitro and in vivo , as well as the nuclear translocation and tyrosine phosphorylation of Stat6 and Jak1 activation, essential downstream targets of IL-4 signaling. Moreover, PKCζ –/– mice display dramatic inhibition of ovalbumin-induced allergic airway disease, strongly suggesting that PKCζ can be a therapeutic target in asthma.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0501202102
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
2005
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12
