Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1126/science.1186068

Type

Journal article

Journal

Science (New York, N.Y.)

Publication Date

04/2010

Volume

328

Pages

372 - 376

Addresses

Molecular Pathogenesis Program, Helen and Martin Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.

Keywords

T-Lymphocyte Subsets, Animals, Mice, Inbred C57BL, Humans, Mice, Arthritis, Rheumatoid, Colitis, Inflammation, Isoenzymes, Protein Kinase C, Tumor Necrosis Factor-alpha, Receptors, Antigen, T-Cell, Enzyme Inhibitors, Lymphocyte Activation, Signal Transduction, Adolescent, Adult, Aged, Middle Aged, T-Lymphocytes, Regulatory, Interferon-gamma, Immunological Synapses, Young Adult, Feedback, Physiological