Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

J Clin Invest. 2015 Jun;125(6):2211-9. doi: 10.1172/JCI78085. Epub 2015 May 11.


Cytokines play a critical role in controlling the differentiation of CD4 Th cells into distinct subsets, including IL-17-producing Th17 cells. Unfortunately, the incidence of a number of autoimmune diseases, particularly those in which the IL-23/IL-17 axis has been implicated, has risen in the last several decades, suggesting that environmental factors can promote autoimmunity. Here we review the role of cytokines in Th17 differentiation, particularly the role of IL-23 in promoting the differentiation of a pathogenic subset of Th17 cells that potently induce autoimmune tissue inflammation. Moreover, we highlight emerging data that indicate that environmental factors, including the intestinal microbiota and changes in diet, can alter normal cytokine regulation with potent effects on Th17 differentiation and thus promote autoimmunity, which has strong implications for human disease.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Cell Differentiation / immunology*
  • Environmental Exposure / adverse effects*
  • Humans
  • Interleukin-17 / immunology
  • Interleukin-23 / immunology
  • Intestines* / immunology
  • Intestines* / microbiology
  • Microbiota / immunology*
  • Th17 Cells / immunology*
  • Th17 Cells / pathology


  • Interleukin-17
  • Interleukin-23