First Author | Zanin-Zhorov A | Year | 2010 |
Journal | Science | Volume | 328 |
Issue | 5976 | Pages | 372-6 |
PubMed ID | 20339032 | Mgi Jnum | J:159102 |
Mgi Id | MGI:4441216 | Doi | 10.1126/science.1186068 |
Citation | Zanin-Zhorov A, et al. (2010) Protein kinase C-theta mediates negative feedback on regulatory T cell function. Science 328(5976):372-6 |
abstractText | 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. |