title: PKC-θ function at the immunological synapse: prospects for therapeutic targeting.
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.
authors: Molecular Pathogenesis Program, Helen and Martin Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors: Alexandra
authors: A
authors: Zanin-Zhorov
authors: Michael L
authors: ML
authors: Dustin
authors: Bruce R
authors: BR
authors: Blazar
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism*; D007167:Immunotherapy / Q000639:trends; D008213:Lymphocyte Activation; D058990:Molecular Targeted Therapy; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011493:Protein Kinase C