PKC-θ function at the immunological synapse: prospects for therapeutic targeting

Trends Immunol. 2011 Aug;32(8):358-63. doi: 10.1016/j.it.2011.04.007. Epub 2011 Jul 4.

Abstract

Protein kinase C (PKC)-θ regulates conventional effector T (Teff) cell function. Since this initial finding, it has become clear that the role of PKC-θ in T cells is complex. PKC-θ plays a central role in Teff cell activation and survival, and negatively regulates stability of the immunological synapse (IS). Recent studies demonstrated that PKC-θ is required for the development of natural CD4(+)Foxp3(+) regulatory T (Treg) cells, and mediates negative regulation of Treg cell function. Here, we examine the role of PKC-θ in the IS, evidence for its distinct localization in Treg cells and the therapeutic implications of inhibiting PKC-θ in Teff cells, to reduce effector function, and in Treg cells, to increase suppressor function, for the prevention and treatment of autoimmune and alloimmune disease states.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Humans
  • Immunological Synapses / metabolism*
  • Immunotherapy / trends
  • Lymphocyte Activation
  • Molecular Targeted Therapy
  • Protein Kinase C / immunology
  • Protein Kinase C / metabolism*
  • Receptor-CD3 Complex, Antigen, T-Cell / metabolism
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Receptor-CD3 Complex, Antigen, T-Cell
  • Protein Kinase C