Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. 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




Journal article



Publication Date





372 - 376


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