Beating Off the Attack in RA

Although the exact causes of autoimmune diseases such as rheumatoid arthritis are unknown, tissue damage is mediated, at least in part, by the (inappropriate) action of effector T cells. Regulatory T cells are a specialised population of T cells which play a role in ‘self-tolerance’ by suppressing activation of other immune cells: genetic deficiency in regulatory T cells causes severe autoimmune disease in both mice and humans.

Researchers at NYU Langone Medical Center examined blood samples from 25 patients with rheumatoid arthritis and found that regulatory T cell function was inversely correlated with disease severity. The team have now discovered a way to enhance the activity of regulatory T cells which may eventually lead to new treatments for autoimmune diseases such as rheumatoid arthritis or inflammatory diseases such as Crohn’s disease.

In effector T cells, the calcium-independent protein kinase C, PKC-θ, localises at the site of contact between the T cell and the antigen presenting cell, placing it in the proximity of other enzymes that mediate T cell activation. When regulatory T cells become activated, however, the team found that PKC-θ is localised away from the point of cell-cell contact. In cell culture experiments, PKC-θ inhibitors were shown to boost the activity of regulatory T cells around 5-fold. One of the inhibitors was also shown to be protective in a mouse model of Crohn’s disease.

The study is published in Science Express and the PKC-θ inhibitors were provided by Boehringer-Ingelheim Pharmaceuticals, Inc.