RORγt protein modifications and IL-17-mediated inflammation

Trends Immunol. 2021 Nov;42(11):1037-1050. doi: 10.1016/ Epub 2021 Oct 9.


RORγt, the master transcription factor for cytokine interleukin (IL)-17, is expressed explicitly in Th17 cells, γδT cells, and type 3 innate lymphoid cells in mice and humans. Since dysregulated IL-17 expression is strongly linked to several human inflammatory diseases, the RORγt-IL-17 axis has been the focus of intense research. Recently, several studies have shown that RORγt is modified by multiple post-translational mechanisms, including ubiquitination, acetylation, SUMOylation, and phosphorylation. This review discusses how post-translational modifications modulate RORγt function and its turnover to regulate IL-17-driven inflammation. Broad knowledge of these pathways is crucial for a clear understanding of the pathogenic role of RORγt+IL-17+ cells and for the development of putative therapeutic strategies to target IL-17-driven diseases such as multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease.

Keywords: IL-17; RORγt; Th17; autoimmune diseases; post-translational modifications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Humans
  • Immunity, Innate
  • Inflammation / metabolism
  • Interleukin-17* / metabolism
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3* / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3* / metabolism
  • Protein Processing, Post-Translational
  • Th17 Cells


  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3