Th17 cell development: from the cradle to the grave

Summary T cells surviving the clonal selection process emigrate from the thymus to the periphery as immature naive T cells. In the periphery, upon activation under specific cytokine milieus, naive T cells adopt specific effector phenotypes, e.g. T‐helper 1 (Th1), Th2, or Th17, and acquire diverse functions to control a myriad of pathogens, tissue injuries, and other immunological insults. Interleukin‐23 ( IL ‐23) is one of the key cytokines that shapes the development and function of Th17 cells with characteristic expression of retinoic acid receptor‐related orphan receptor γ‐t ( ROR γt), IL ‐17, IL ‐22, and granulocyte macrophage colony‐stimulating factor ( GM ‐ CSF ). More recently, emerging data suggest that IL ‐23 also promotes development of ‘natural Th17’ (nTh17) cells that arise from the thymus, analogous to natural regulatory T cells (nTreg). We are just beginning to understand the unique thymic developmental path of nTh17 cells, which are distinct from antigen‐experienced memory Th17 cells. In this review, we explore the differentiation and function of inducible, natural, and memory Th17 subsets, which encompass a broad range of immune functions while maintaining tissue hemostasis, and highlight the participation of IL‐23 during the life cycle of Th17 cells.