TGF-β1 is synthesized in cells as a 390-amino acid protein. Furin cleaves the protein at residue 278, yielding an N-terminal cleavage product which corresponds to the latency-associated peptide (LAP), and the 25 kD C-terminal portion of the precursor constitutes the mature TGF-β1. In addition to furin, some other activators can release TGF-β from LAP. TGF-β activators include proteases that degrade LAP, thrombospondin-1, reactive oxygen species, and the integrins αvβ6 and αvβ8. Mouse TGF-β converts na?ve T cells into regulatory T (Treg) cells that prevent autoimmunity. However, human TGF-β1 seems not to take part in T reg differentiation. Th17 murine can be induced from na?ve CD4+ T cells by the combination of TGF-β1 and IL-6 or IL-21. Nevertheless, the regulation of human Th17 differentiation is distinct. TGF-β1 seems to have dual effects on human Th17 differentiation in a dose-dependent manner. While TGF-β1 is required for the expression of RORct, in human naive CD4+ T cells from cord blood, TGF-β1 can inhibit the function of RORct at high doses. By using serum-free medium, it has been clarified that the optimum conditions for human Th17 differentiation are TGF-β1, IL-1β, and IL-2 in combination with IL-6, IL-21 or IL-23.