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Publication : Control of T helper 2 cell function and allergic airway inflammation by PKCzeta.

First Author  Martin P Year  2005
Journal  Proc Natl Acad Sci U S A Volume  102
Issue  28 Pages  9866-71
PubMed ID  15987782 Mgi Jnum  J:99860
Mgi Id  MGI:3584076 Doi  10.1073/pnas.0501202102
Citation  Martin P, et al. (2005) Control of T helper 2 cell function and allergic airway inflammation by PKCzeta. Proc Natl Acad Sci U S A 102(28):9866-71
abstractText  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. PKCzeta has been implicated in the regulation of apoptosis and NF-kappaB, as well as in the control of T-dependent responses, although no defects were detected in naive T cells from PKCzeta-/- mice. Here, we report that PKCzeta is critical for IL-4 signaling and Th2 differentiation. Thus, PKCzeta levels are increased during Th2 differentiation, but not Th1 differentiation, of CD4+ T cells, and the loss of PKCzeta 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, PKCzeta-/- mice display dramatic inhibition of ovalbumin-induced allergic airway disease, strongly suggesting that PKCzeta can be a therapeutic target in asthma.
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