Th17 cell differentiation: The long and winding road

The characterization of the new lineage of IL-17-producing CD4(+) T helper (Th17) cells has revolutionized our current understanding of T cell-mediated immunity. Over the past five years, there have been many twists and turns as the pathways that lead to Th17 cell differentiation have been elucidated. Not least of these was the discovery that TGF-beta is a crucial cytokine for Th17 cell development, suggesting that Th17 and regulatory T cell subsets share reciprocal developmental pathways during the pathogenesis or control of inflammation. This review aims to bring together the observations that have formed current opinion on factors that promote and contain Th17 cell development, in both mouse and man. Unresolved controversies in this field are also discussed: For example, IL-23 is absolutely required for disease pathogenesis in many models of Th17-cell-mediated autoimmunity, yet its role in Th17 cell development is relatively unclear.