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

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

Alexandra Zanin-Zhorov  1 , Michael L Dustin, Bruce R Blazar
Affiliations
Review

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

Alexandra Zanin-Zhorov et al. Trends Immunol. 2011 Aug.

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.

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Figures

Figure 1
Figure 1
Signaling molecules linking the TCR to NF-κB activation in T cells.
Figure 2
Figure 2
Immunological synapse (IS) stability and localization of NF-κB activating complex in Teff and Treg cells. The NF-κB activating complex consisting of PKC-θ, Carma-1 and other components is localized to the center of the IS in Teff and the distal pole complex in Treg. The IS is destabilized by PKC-θ in Teff leading to more broken IS patterns, whereas exclusion of PKC-θ from the IS of Treg stabilizes there IS. Red = ICAM-1, green = TCR, white = actin.
Figure 3
Figure 3
See this image and copyright information in PMC

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