Loss of PKCλ/ι impairs Th2 establishment and allergic airway inflammation in vivo
Author(s) -
JunQi Yang,
Michael Leitges,
Angeles Durán,
Marı́a T. Diaz-Meco,
Jorge Moscat
Publication year - 2009
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0805907106
Subject(s) - microbiology and biotechnology , conditional gene knockout , t cell , transcription factor , biology , inflammation , knockout mouse , protein kinase c , cytokine , ex vivo , immunology , in vivo , signal transduction , immune system , phenotype , gene , genetics
The differentiation of T cells along different lineages is central to the control of immunity. Here we have used a conditional gene knockout system to delete PKC lambda/iota selectively in activated T cells. With this system we have demonstrated that PKC lambda/iota is necessary for T-helper cell (Th2) cytokine production and optimal T-cell proliferation and allergic airway inflammation in vivo. Our data demonstrate that the activation of the transcription factors nuclear factor of activated T cells and NF-kappaB is impaired in PKC lambda/iota-deficient activated T cells. In addition, we present genetic knockout evidence in ex vivo experiments with primary T cells that PKC lambda/iota is critical for the control of cell polarity during T-cell activation. Therefore PKC lambda/iota emerges as a critical regulator of Th 2 activation.
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