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The purpose of this review is to summarize the most recent discoveries in the field of phenotypic and functional characterization of human and murine Th17 cells.Human Th17 cells express CD161 and exclusively originate from CD161+ precursors present in umbilical cord blood and newborn thymus in response to the combined activity of IL-1β and IL-23. On the contrary, murine Th17 cells do not express CD161 and originate in response to IL-6, IL-1, and TGF-β, even if the latter has recently been shown to be dispensable. Studies in mice have initially suggested that Th17 cells are the pathogenic cells in autoimmune disorders, whereas Th1 cells may behave rather as protective. Studies in humans have subsequently demonstrated the capacity of Th17 cells to shift to Th1 cells when activated in the presence of IL-12. The plasticity of Th17 to Th1 cells has been now confirmed in mice, where it was found that Th17 cells become pathogenic in some models of autoimmune diseases only when they shift to Th1 cells.The issue of Th17 plasticity is of fundamental importance for those researchers directed to manipulate immune responses in therapeutically useful manner.