CD4+ T helper (TH) cells now include different types based on their cytokine and transcription factor signatures: the cytokines interleukin (IL)-12 and interferon (IFN)-γ and the transcription factors STAT1, STAT4 and T-bet promote the development of TH1 cells, which produce IFN-γ as their ‘signature’ cytokine. The cytokine IL-4, together with the transcription factors STAT6 and GATA3, promotes the development of TH2 cells, which produce IL-4, IL-5 and IL-13[1, 2]. Natural regulatory T (nTreg) cells, which develop in the thymus, gained acceptance as a bona fide CD4+ T cell lineage with the discovery that the transcription factor Foxp3 directs their development. Induced Treg (iTreg) cells are generated by transforming growth factor (TGF)-β and retinoic acid in the periphery and, like nTreg cells, can produce TGF-β, IL-10 and IL-35. Follicular helper T (TFH) cells can develop under the influence of IL-6 by the induction of the transcription factor Bcl-6 . Largely through their capacity to induce expression of the transcription factors related orphan receptor-γt (RORγt), RORα and STAT3, the cytokines TGF-β, IL-6 and IL-23 promote the development of TH17 cells, which produce IL-17A, IL-17F and IL-22. IL-21 is principally a product of TH17 and TFH cells and further promotes, through an autocrine feedback loop, the development of these cells [5–7]. The differentiation of TH17 cells from naïve CD4+ T cells is regulated directly by cytokines and transcriptional factors and indirectly by other immune cells [5, 7]. TGF-β and IL-6, broadly expressed by many cell types, including dendritic cells (DCs) and epithelial cells, are dominant in the initiation of TH17 cell differentiation. IL-23, IL-1β and IL-21, which are products of activated DCs, macrophages, activated T cells or inflamed epithelial cells, possibly expand and maintain the differentiated TH17 cells in the presence of IL-6 and TGF-β1. TH17 cells appear to be key effector T cells in a variety of human inflammatory and autoimmune diseases as well as in experimental animal models. Therefore, to totally understand the accurate immunoregulatory mechanism of TH17 cells, this should become an important research issue.