Loss of PKC lambda/iota impairs Th2 establishment and allergic airway inflammation in vivo

Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1099-104. doi: 10.1073/pnas.0805907106. Epub 2009 Jan 14.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Polarity
  • Cell Proliferation
  • Cytokines / metabolism
  • Hypersensitivity / enzymology*
  • Hypersensitivity / immunology*
  • Immunoglobulin E / blood
  • Inflammation / enzymology*
  • Inflammation / immunology
  • Isoenzymes / deficiency*
  • Isoenzymes / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Ovalbumin
  • Protein Kinase C / deficiency*
  • Protein Kinase C / metabolism
  • Respiratory System / enzymology
  • Respiratory System / immunology
  • Respiratory System / pathology*
  • Th2 Cells / cytology
  • Th2 Cells / enzymology*
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Transcription Factors / metabolism
  • Up-Regulation

Substances

  • Cytokines
  • Isoenzymes
  • Transcription Factors
  • Immunoglobulin E
  • Ovalbumin
  • Protein Kinase C
  • protein kinase C lambda