Th17 cell development: from the cradle to the grave

Immunol Rev. 2013 Mar;252(1):78-88. doi: 10.1111/imr.12036.


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 (RORγt), 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Gene Expression Regulation / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-23 / genetics
  • Interleukin-23 / immunology*
  • Interleukins / genetics
  • Interleukins / immunology
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology*
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th17 Cells / cytology
  • Th17 Cells / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology


  • Interleukin-17
  • Interleukin-23
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • interleukin-22