IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes

J Invest Dermatol. 2020 Jul;140(7):1379-1389.e2. doi: 10.1016/j.jid.2019.12.013. Epub 2020 Jan 18.


Our group has recently shown that keratinocyte-derived IL-17E (IL-25), one of six members of the IL-17 family, is overexpressed in lesional psoriatic skin and is involved in its pathophysiology. We show here that IL-22 enhances IL-17E production in human keratinocytes and that these cells display a complete IL-17E receptor at their surface, the expression of which is further induced by IL-17A, indicating a potential autocrine effect of IL-17E. Therefore, we addressed the impact of IL-17E on the function of human primary keratinocytes. IL-17E promoted the proliferation of keratinocytes in two-dimensional and three-dimensional cultures and caused the concomitant upregulation of differentiation-associated gene transcripts (e.g., keratin 10), whereas their expression was either inhibited or not changed by IL-17A. Contrary to IL-17A, IL-17E was not involved in the induction of antimicrobial proteins. Time-lapse analysis of cell movement showed that IL-17E influences cell motility, increasing both cell speed and displacement. This was associated with specific changes in the actin cytoskeleton organization and the cell-substrate adhesion. No such effects were observed upon IL-17A stimulation. In summary, we identified effects of IL-17E clearly distinct from IL-17A, pointing toward an important role of IL-17E in the physiology and pathophysiology of the epidermis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Adult
  • Antimicrobial Cationic Peptides / metabolism
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Epidermis / metabolism*
  • Humans
  • Interleukin-17 / metabolism*
  • Keratinocytes / metabolism*
  • Psoriasis / metabolism
  • Skin / metabolism
  • Up-Regulation


  • Antimicrobial Cationic Peptides
  • IL17A protein, human
  • IL25 protein, human
  • Interleukin-17