2. Academic Validation
  3. IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes

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.
Julia Borowczyk 1,  Claudia Buerger 2,  Neschaat Tadjrischi 2,  Justyna Drukala 3,  Michal Wolnicki 4,  Dawid Wnuk 3,  Ali Modarressi 5,  Wolf-Henning Boehncke 6,  Nicolò Costantino Brembilla 7
Affiliations

Affiliations

  • 1 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • 2 Department of Dermatology, Clinic of the Goethe-University, Frankfurt am Main, Germany.
  • 3 Cell Bank, Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.
  • 4 Department of Pediatric Urology, Jagiellonian University Medical College, Cracow, Poland.
  • 5 Plastic, Reconstructive and Aesthetic unit, University Hospitals of Geneva and School of Medicine, Geneva, Switzerland.
  • 6 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Division of Dermatology and Venereology, University Hospitals of Geneva, Geneva, Switzerland.
  • 7 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. Electronic address: nicolo.brembilla@unige.ch.
PMID: 31958433 DOI: 10.1016/j.jid.2019.12.013
Abstract

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.

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