Differential requirement of PKC-θ in the development and function of natural regulatory T cells

Sonal Gupta, Santhakumar Manicassamy, Chenthamarakshan Vasu, Anvita Kumar, Weirong Shang, Zuoming Sun

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

CD4+CD25+ natural Treg cells, which are developed in the thymus, migrate to the periphery to actively maintain self-tolerance. Similar to conventional T cells, TCR signals are critical for the development and activation of Treg cell inhibitory function. While PKC-θ-mediated TCR signals are required for the activation of peripheral naïve T cells, they are dispensable for their thymic development. Here, we show that mice deficient in PKC-θ had a greatly reduced number of CD4+Foxp3+ Treg cells, which was independent of PKC-θ-regulated survival, as transgenic Bcl-xL could not restore the Treg cell population in PKC-θ-/- mice. Active and WT PKC-θ markedly stimulated, whereas inactive PKC-θ and dominant negative NFAT inhibited Foxp3 promoter activity. In addition, mice-deficient in calcineurin Aβ had a decreased Treg cell population, similar to that observed in PKC-θ deficient mice. It is likely that PKC-θ promoted the development of Treg cells by enhancing Foxp3 expression via activation of the calcineurin/NFAT pathway. Finally, Treg cells deficient in PKC-θ were as potent as WT Treg cells in inhibiting T cell activation, indicating that PKC-θ was not required for Treg cell-mediated inhibitory function. Our data highlight the contrasting roles PKC-θ plays in conventional T cell and natural Treg cell function.

Original languageEnglish (US)
Pages (from-to)213-224
Number of pages12
JournalMolecular Immunology
Volume46
Issue number2
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

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Keywords

  • CD4+CD25+ cells
  • PKC-θ
  • Survival
  • T cell development

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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