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PMID:15987782

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Citation

Martin, P, Villares, R, Rodriguez-Mascarenhas, S, Zaballos, A, Leitges, M, Kovac, J, Sizing, I, Rennert, P, Márquez, G, Martínez-A, C, Diaz-Meco, MT and Moscat, J (2005) Control of T helper 2 cell function and allergic airway inflammation by PKCzeta. Proc. Natl. Acad. Sci. U.S.A. 102:9866-71

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.

Links

PubMed PMC1174981 Online version:10.1073/pnas.0501202102

Keywords

Animals; Asthma/immunology; Asthma/physiopathology; Bronchial Hyperreactivity/chemically induced; Bronchial Hyperreactivity/immunology; Cell Differentiation/physiology; Cytokines/metabolism; Flow Cytometry; Fluorescent Antibody Technique; Inflammation/immunology; Interleukin-4/metabolism; Isoenzymes/metabolism; Mice; Mice, Knockout; Ovalbumin/toxicity; Protein Kinase C/metabolism; Signal Transduction/immunology; Th2 Cells/immunology; Th2 Cells/metabolism; Th2 Cells/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KPCZ

involved_in

GO:0032754: positive regulation of interleukin-5 production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KPCZ

involved_in

GO:0032753: positive regulation of interleukin-4 production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KPCZ

involved_in

GO:0032736: positive regulation of interleukin-13 production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KPCZ

involved_in

GO:0032733: positive regulation of interleukin-10 production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KPCZ

involved_in

GO:2000553: positive regulation of T-helper 2 cell cytokine production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KPCZ

involved_in

GO:0045630: positive regulation of T-helper 2 cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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