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Protein kinase C-theta mediates negative feedback on regulatory T cell function.

ABSTRACT: T cell receptor (TCR)-dependent regulatory T cell (Treg) activity controls effector T cell (Teff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Protein kinase C-theta (PKC-theta) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-theta was sequestered away from the Treg immunological synapse. Furthermore, PKC-theta blockade enhanced Treg function, demonstrating PKC-theta inhibits Treg-mediated suppression. Inhibition of PKC-theta protected Treg from inactivation by TNF-alpha, restored activity of defective Treg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. Treg freed of PKC-theta-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases.

SUBMITTER: Zanin-Zhorov A

PROVIDER: S-EPMC2905626 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Protein kinase C-theta mediates negative feedback on regulatory T cell function.

Zanin-Zhorov Alexandra A Ding Yi Y Kumari Sudha S Attur Mukundan M Hippen Keli L KL Brown Maryanne M Blazar Bruce R BR Abramson Steven B SB Lafaille Juan J JJ Dustin Michael L ML

Science (New York, N.Y.) 20100325 5976

T cell receptor (TCR)-dependent regulatory T cell (Treg) activity controls effector T cell (Teff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Protein kinase C-theta (PKC-theta) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-theta was sequestered away from the Treg immunological synapse. Furthermore, PKC-theta blockade enhanced Treg function, demonstrating PKC-theta inhibits Treg-mediated suppress ...[more]

PMID: 20339032

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