Inhibiting the inhibitor of the inhibitor: blocking PKC-theta to enhance regulatory T cell function.
Protein kinase C (PKC-theta), one of many PKC isoforms expressed in T cells, is important for the activation of mature effector T cells. During T cell activation, PKC-theta is recruited to the interface between the T cell and the activating cellular interaction partner, the antigen-presenting cell or a synthetic substitute thereof. New evidence establishes that PKC-theta function differs in regulatory T cells, a T cell subset that suppresses the function of effector T cells. In regulatory T cells, PKC-theta inhibits their function and, intriguingly, is sequestered from the activating cellular interface. This finding raises several questions of general interest. Does PKC-theta function overlap with that of other PKC family members? What are the functionally critical distinctions in the similar signaling systems of effector and regulatory T cells? Does the divergent localization of PKC-theta in regulatory T cells drive function?
Roybal
Kole T
KT
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Wülfing
Christoph
C
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008954:Models, Biological; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D000099221:Protein Kinase C zeta
D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta