In inflammatory conditions such as RA, the neutrophil has tended to be dismissed as a short-lived, terminally differentiated, irrelevant bystander cell. However, this is clearly not the case. A better understanding of the complex heterogeneous pathways and processes that constitute RA, in parallel with a more sophisticated knowledge of neutrophil biology has identified many potential roles for these cells in the persistence of inflammation and progression of joint damage, which should not be underestimated. Not only are neutrophils found in high numbers within the rheumatoid joint, both in synovial tissue and in joint fluid, they have a huge potential to directly inflict damage to tissue, bone and cartilage via the secretion of proteases and toxic oxygen metabolites, as well as driving inflammation through antigen presentation and secretion of cytokines, chemokines, prostaglandins and leucotrienes. Drugs already used to treat RA down-regulate many neutrophil functions, including migration to the joint, degranulation and production of inflammatory mediators, and these cells should be considered as important targets for the development of new therapies in the future.

The discovery of regulatory T cells almost 15 years ago initiated a new and exciting research area. The growing evidence for a critical role of these cells in controlling autoimmune responses has raised expectations for therapeutic application of regulatory T cells in patients with autoimmune arthritis. Here, we review recent studies investigating the presence, phenotype and function of these cells in patients with RA and juvenile idiopathic arthritis (JIA) and consider their therapeutic potential. Both direct and indirect methods to target these cells will be discussed. Arguably, a therapeutic approach that combines multiple regulatory T-cell-enhancing strategies could be most successful for clinical application.