Origin and plasticity of human and murine Th17 cells. Human Th17 cells originate from a small subset of CD4⁺CD161⁺ T-cell precursors present in newborn thymus and UCB, which already express RORC, IL-23R, IL-1RI, and CCR6.³⁷  (This account of the origin of human Th17 cells mainly reflects a personal view and does not take into account all the data presently available in the literature.) These cells differentiate in vitro in response to the combined activity of IL-1β and IL-23 into mature Th17 cells, which express RORC, T-bet, IL-12Rβ2, CD161,³⁷  and CCR6,^32,33  but under the same conditions can also give rise to Th17/Th1 and Th1 cells, which express T-bet³³  and CXCR3.^32,38  In the presence of IL-12, T-bet expression is up-regulated in Th17 cells, which shift to the production of IFN-γ.³³  Murine Th17 cells originate from a naive Th cell in response to the combined activity of TGF-β and IL-6,^12-14  which induce ROR-γt,^17,18  IL-23R,^12-14,17,18  and CCR6³⁶  expression, but the early IL-1 signaling seems also to be critical for their differentiation.³⁹  IL-23 appears to be required for the survival and/or expansion of murine Th17 cells.^12-14,17,18  However, in response to IL-12 or of the prolonged activity of IL-23, these cells up-regulate T-bet and shift to cells producing IFN-γ both in vitro and in vivo.⁴⁰