Differentiation of naive CD4+ T cells into Tregs following induction by TGF-β1 alone. TGF-β1 and IL-6 promote jointly the differentiation of the naive CD4+ T cells into Th17s, while IL-6 inhibits the TGF-β-induced Treg generation. Th17s secreted IL-17 to further promote the release of cytokines such as IL-6 and TNF and other inflammatory cell activators, leading to a waterfall-like overlay effect. Treg, regulatory T cell; Th17, T helper 17 cell; CD4, cluster of differentiation 4; IL, interleukin; TGF-β1, transforming growth factor-β1; TNF, tumor necrosis factor.