Anti-inflammatory neutrophil functions in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the immune system attacks joints, e.g. in hands and knees, causing pain and disability unless treated successfully. Without known cure, RA affect 1% of the UK population. Neutrophils, very common immune cells in humans, are essential for fighting infections, generating inflammation in the process. They are tightly controlled, but if this control goes awry, they can drive serious tissue damage, e.g. in RA. Neutrophils are key to the generation of inflammation. Intriguingly, research suggests that they are also required for tissue repair: When a threat is eliminated, neutrophils instruct macrophages to turn from pro- to anti-inflammatory. Recent research suggests neutrophils can also modulate T cells, which in RA also attack joint tissue. If stimulated excessively, T cells may become unresponsive, or ‘exhausted’, a positive thing in autoimmunity. This project hypothesizes that neutrophils have some anti-inflammatory functions even in the inflamed joint in RA. To test this hypothesis, neutrophils from healthy human volunteers will be treated to resemble those in the inflamed joint in RA. Their ability to perform a range of anti-inflammatory functions, alone, and in conjunction with macrophages and T cells will be examined. The proposed work will help with understanding immune cell cross-talk in RA and may inform the design of improved therapies for people with RA.