The potential role of Th17 in mediating the transition from acute to chronic autoimmune inflammation: rheumatoid arthritis as a model.

T helper 17 cells (Th17) have arisen in the last 15 years as major effector cells in several chronic inflammatory states. In synovitis associated with rheumatoid arthritis (RA), Th17 emerged as being involved in driving the active acute phases and correlated with local and systemic parameters of inflammation; in particular, TCRζ(dim) Th17 appear to be the greatest producers of IL-17 at the single-cell level. IL-1beta and IL-6, along with IL-23, arose as the major drivers of differentiation and local development of Th17, while IL-15 and cell-cell contact can trigger the local production of IL-17. TNF-alpha inhibition can reversibly block the migration of pathogenic effector memory TCRzeta(dim) T cells and CCR6+ Th17 from peripheral blood to inflamed tissues. IL-17 is a potent chemoattractant for pre-committed CD4+ T cells and neutrophils, and may promote the migration of B cells to lymphoid follicles in the chronic phase of synovial inflammation. Importantly, IL-17 drives osteoclastogenesis and neoangiogenesis in the RA joint. These data strongly suggest that Th17 are key effector cells in driving the transition from the acute to the chronic phase of RA inflammation.