Protein kinase C theta is dispensable for suppression mediated by CD25+CD4+ regulatory T cells

PLoS One. 2017 May 22;12(5):e0175463. doi: 10.1371/journal.pone.0175463. eCollection 2017.

Abstract

The activation of conventional T cells upon T cell receptor stimulation critically depends on protein kinase C theta (PKCθ). However, its role in regulatory T (Treg) cell function has yet to be fully elucidated. Using siRNA or the potent and PKC family-selective pharmacological inhibitor AEB071, we could show that murine Treg-mediated suppression in vitro is independent of PKCθ function. Likewise, Treg cells of PKCθ-deficient mice were fully functional, showing a similar suppressive activity as wild-type CD25+CD4+ T cells in an in vitro suppression assay. Furthermore, in vitro-differentiated wild-type and PKCθ-deficient iTreg cells showed comparable Foxp3 expression as well as suppressive activity. However, we observed a reduced percentage of Foxp3+CD25+ CD4+ T cells in the lymphatic organs of PKCθ-deficient mice. Taken together, our results suggest that while PKCθ is involved in Treg cell differentiation in vivo, it is dispensable for Treg-mediated suppression.

MeSH terms

  • Animals
  • CD4 Antigens / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Forkhead Transcription Factors / metabolism*
  • In Vitro Techniques
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Protein Kinase C / genetics*
  • Protein Kinase C / metabolism
  • Protein Kinase C-theta
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology
  • Thymocytes / cytology
  • Thymocytes / immunology

Substances

  • CD4 Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Il2ra protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Isoenzymes
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta