Transcriptional Regulators of T Helper 17 Cell Differentiation in Health and Autoimmune Diseases

Front Immunol. 2020 Mar 12:11:348. doi: 10.3389/fimmu.2020.00348. eCollection 2020.

Abstract

T helper (Th) 17 cells are a subtype of CD4 T lymphocytes characterized by the expression of retinoic acid-receptor (RAR)-related orphan receptor (ROR)γt transcription factor, encoded by gene Rorc. These cells are implicated in the pathology of autoimmune inflammatory disorders as well as in the clearance of extracellular infections. The main function of Th17 cells is the production of cytokine called interleukin (IL)-17A. This review highlights recent advances in mechanisms regulating transcription of IL-17A. In particular, we described the lineage defining transcription factor RORγt and other factors that regulate transcription of Il17a or Rorc by interacting with RORγt or by binding their specific DNA regions, which may positively or negatively influence their expression. Moreover, we reported the eventual involvement of those factors in Th17-related diseases, such as multiple sclerosis, rheumatoid arthritis, psoriasis, and Crohn's disease, characterized by an exaggerated Th17 response. Finally, we discussed the potential new therapeutic approaches for Th17-related diseases targeting these transcription factors. The wide knowledge of transcriptional regulators of Th17 cells is crucial for the better understanding of the pathogenic role of these cells and for development of therapeutic strategies aimed at fighting Th17-related diseases.

Keywords: Crohn's disease; T helper 17 cells; interleukin-17; multiple sclerosis; psoriasis; retinoic acid receptor related orphan nuclear receptor γt; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoimmune Diseases / immunology*
  • Basic-Leucine Zipper Transcription Factors / physiology
  • Cell Differentiation
  • Gene Expression Regulation*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology
  • Interleukin-17 / genetics*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / physiology*
  • STAT3 Transcription Factor / physiology
  • Th17 Cells / cytology
  • Th17 Cells / physiology*
  • Transcription, Genetic

Substances

  • BATF protein, human
  • Basic-Leucine Zipper Transcription Factors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • STAT3 Transcription Factor