Dr Richard Williams

The principle objective of our work is to understand and exploit endogenous anti-inflammatory pathways in order to develop new treatments for rheumatoid arthritis and other autoimmune diseases. At present we are working on the following avenues of research.

1. Combination therapy. Anti-TNF therapy has proved to be very effective in controlling inflammation in RA but, increasingly, treatment is aimed towards achieving remission. We have recently discovered that TNF blockade in experimental arthritis leads, unexpectedly, to an increase in numbers of pathogenic Th17 cells and increased IL-17 production, suggesting that TNF plays a negative feedback role in arthritis. Hence, our current studies are aimed at demonstrating that the therapeutic effects of anti-TNF can be improved by concurrent treatment with anti-IL-17.

2. Estrogen receptor ligands. Estrogens play a dominant role in the development and maintenance of the female reproductive system and are also known to influence such diverse processes as bone resorption and CNS function. It has also become apparent in recent years that estrogens have profound effects on cells of the immune and inflammatory systems and clinical observations indicate that a number of autoimmune diseases may go into remission during pregnancy. Estrogens mediate their effects via one of two receptors, ERα and ERβ, and we are currently investigating the possibility that activators of ERβ will be useful therapeutic agents for rheumatoid arthritis.

3. Induction of tolerance. Antigen presenting cells possess multiple mechanisms for regulating the effector function of T lymphocytes and are often regarded as a bridge between the innate and adaptive immune response We are developing a construct consisting of a mutated version of the MHC class II invariant chain in which the CLIP sequence has been substituted for epitopes known to be important in autoimmunity. This will be used to direct the differentiation of T cells away from a pathogenic response and towards a regulatory response by expressing CLIP substituted invariant chain in combination with one of a number of key intracellular signalling molecules that are known to modulate antigen presenting cell function.