Loss of PKC lambda/iota impairs Th2 establishment and allergic airway inflammation in vivo.
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.
Yang
Jun-Qi
JQ
Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Leitges
Michael
M
Duran
Angeles
A
Diaz-Meco
Maria T
MT
Moscat
Jorge
J
D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D006967:Hypersensitivity / Q000201:enzymology* / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000201:enzymology* / Q000276:immunology; D007527:Isoenzymes / Q000172:deficiency* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin; D011493:Protein Kinase C / Q000172:deficiency* / Q000378:metabolism; D012137:Respiratory System / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D018418:Th2 Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D000099293:Protein Kinase C-lambda
D016207:Cytokines; D007073:Immunoglobulin E; D007527:Isoenzymes; D010047:Ovalbumin; D011493:Protein Kinase C; D014157:Transcription Factors; D000099293:Protein Kinase C-lambda