Unknown

Dataset Information

0

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 |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC2667369 | biostudies-literature
| S-EPMC4040250 | biostudies-literature
| S-EPMC7474270 | biostudies-literature
| S-EPMC4445242 | biostudies-literature
| S-EPMC4332157 | biostudies-literature
| S-EPMC3767810 | biostudies-literature
| S-EPMC7544975 | biostudies-literature
| S-EPMC8761795 | biostudies-literature
| S-EPMC5978805 | biostudies-literature
| S-EPMC4496282 | biostudies-literature