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

Protein kinase C (PKC)-theta regulates conventional effector T (Teff) cell function. Since this initial finding, it has become clear that the role of PKC-theta in T cells is complex. PKC-theta plays a central role in Teff cell activation and survival, and negatively regulates stability of the immunological synapse (IS). Recent studies demonstrated that PKC-theta 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-theta in the IS, evidence for its distinct localization in Treg cells and the therapeutic implications of inhibiting PKC-theta 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.