Skin inflammation induced by the synergistic action of IL17A, IL22, OSM, IL1α and TNFα recapitulates some features of psoriasis

The Journal of Immunology, 184(9):5263 -5270


Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, Unités Propres de Recherche, Équipe d’Accueil, Pôle Biologie Santé, Université de Poitiers, France.
Laboratoire Protéines et Inflammation, CHU de Poitiers, France.
Service de Chirurgie Plastique and Service de Dermatologie, CHU de Poitiers, France.
Bioalternatives, Gençay, France.


Keratinocytes play a crucial role in the regulation of skin inflammation, responding to environmental and immune cells stimuli. They produce soluble factors that can act in an autocrine or paracrine manner on immune cells or directly on aggressors. A screening of the activities of 36 cytokines on keratinocyte gene expression identified IL17A, IL22, oncostatin M, TNFalpha, and IL1alpha as potent cytokines in inducing cutaneous inflammation. These five proinflammatory cytokines synergistically increased production of CXCL8 and beta-defensin 2 (BD2).
In addition, ex vivo studies on human skin explants demonstrated upregulation of BD2, S100A7, and CXCL8 expression in response to the same combination of cytokines. In vivo intradermal injection of these five cytokines in mouse increased CXCL1, CXCL2, CXCL3, S100A9, and BD3 expression, associated with neutrophil infiltration. We confirmed and extended this synergistic effect using quantitative real-time PCR analysis and observed increased expression of nine chemokines and 12 antimicrobial peptides. Production of CXCL, CXCL5, and CXCL8 by keratinocytes stimulated in the presence of this cytokine combination was associated with increased neutrophil chemotactic activity. Similarly, high production of BD2, BD3, and S100A7 was associated with an increased antimicrobial activity.
Finally, the transcriptional profile observed in this in vitro model of inflammatory keratinocytes correlated with the one of lesional psoriatic skin. Our results demonstrate the important potentiating activities of IL17A, IL22, oncostatin M, TNFalpha, and IL1alpha on keratinocytes. This is particularly interesting in the context of psoriasis where these cytokines are overexpressed and could synergize to play an important role in upregulation of chemokines and antimicrobial peptides production.

© 2010 by The American Association of Immunologists, Inc.

KEYWORDS: Psoriasis; Skin inflammation; IL17A ; IL22

Check out Bioalternatives’ updates and experience new testing ideas

  • Bioassays, models and services
  • Posts and publications
  • Events
  • The legal basis for the processing is consent. Your e-mail address will only be communicated to the following recipients: the departments concerned and authorised by QIMA LIFE SCIENCE. This data is kept for as long as you are registered to the newsletter.

    You can access your data, rectify it, request its deletion or exercise your right to limit the processing of your data, withdraw your consent to the processing of your data at any time, oppose the processing of your data and you have a right to the portability of your data.

    Visit for more information on your rights.
    You can exercise all your rights using the following linkGestion des droits or by writing to If you feel, after contacting us, that your "Informatique et Libertés" rights are not being respected, you can submit a complaint to the CNIL.

  • The information collected on this form is recorded in a file used by QIMA Life Sciences to send you its newsletter.