Pathway of murine Th17 differentiation. IL-17 producing CD4+ T helper (Th17) cells originate in response to transforming growth factor (TGF)-β and IL-6 produced by dencritic cells (DCs), whereas TGF-β alone in the absence of IL-6 promotes differentiation of the naïve T helper (Th) cell into a Foxp3+ T regulatory (Treg) cell. IL-23 produced by DCs allows the expansion and/or survival of Th17 cells. Th17 cells themselves produce IL-21, which provides an autocrine amplification loop. IFN-γ, IL-4, IL-25 and IL-27 play an inhibitory role in the development of murine Th17 cells. Double parallel lines across the arrow mean inhibitory effect. ROR, orphan retinoid nuclear receptor.