Control of T helper 2 cell function and allergic airway inflammation by PKCzeta.
Proc Natl Acad Sci U S A
; 102(28): 9866-71, 2005 Jul 12.
Article
en En
| MEDLINE
| ID: mdl-15987782
ABSTRACT
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 naïve 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Asma
/
Proteína Quinasa C
/
Transducción de Señal
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Hiperreactividad Bronquial
/
Células Th2
/
Inflamación
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2005
Tipo del documento:
Article
País de afiliación:
España