1. Protein Kinase C-ϑ Mediates Negative Feedback on Regulatory T Cell Function.
- Author
-
Zanin-Zhorov, Alexandra, Ding, Yi, Kumari, Sudha, Attur, Mukundan, Hippen, Keti L., Brown, Maryanne, Blazar, Bruce R., Abramson, Steven B., Lafaille, Juan J., and Dustin, Michael L.
- Subjects
- *
PROTEIN kinases , *T cells , *CYTOKINES , *IMMUNE system , *RHEUMATOID arthritis , *GENE silencing , *LABORATORY mice , *PATIENTS , *GENETICS - 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-α (TNF-α). Protein kinase C-ϑ (PKC-ϑ) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-ϑ was sequestered away from the Treg immunological synapse. Furthermore, PKC-ϑ blockade enhanced Treg function, demonstrating PKC-ϑ inhibits Treg- -mediated suppression. Inhibition of PKC-ϑ protected Treg from inactivation by TNF-α, restored activity of defective Treg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. Treg freed of PKC-ϑ-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF