Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 28, Pages 9866-9871Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0501202102
Keywords
apoptosis; asthma; NF-kappa B
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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. PKC zeta has been implicated in the regulation of apoptosis and NF-kappa B, as well as in the control of T-dependent responses, although no defects were detected in naive T cells from PKC zeta(-/-) mice. Here, we report that PKC zeta is critical for IL-4 signaling and Th2 differentiation. Thus, PKC zeta levels are increased during Th2 differentiation, but not Th1 differentiation, of CD4(+) T cells, and the loss of PKC zeta 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, PKC zeta(-/-) mice display dramatic inhibition of ovalbumin-induced allergic airway disease, strongly suggesting that PKC zeta can be a therapeutic target in asthma.
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