Synergistic induction of IL-23 by TNFα, IL-17A, and EGF in keratinocytes

Benjamin Ehst, Zhiping Wang, Justin Leitenberger, Danielle McClanahan, Rachel De La Torre, Erika Sawka, Alex G. Ortega-Loayza, Jennifer Strunck, Teri Greiling, Eric Simpson, Yuangang Liu

Research output: Contribution to journalArticlepeer-review

Abstract

IL-23 is an inflammatory cytokine that plays an essential role in Th17 immunity by enhancing Th17 cell proliferation and survival, and Th17 cytokine production. IL-23 has pathogenic roles in the development of Th17-mediated inflammatory diseases including psoriasis. Despite successful treatment of psoriasis by blocking IL-23, the regulation of IL-23 expression in psoriasis patients is largely unknown. Dendritic cells are generally considered to be the primary source of IL-23 in psoriasis. While high levels of IL-23 are found in psoriatic epidermis, IL-23 expression in psoriatic keratinoctyes remains a controversial issue. In this study, we demonstrated that IL-23 production is induced by a combination of TNFα and IL-17A in human keratinocytes. Additionally, this IL-23 induction by TNFα and IL-17A is further increased in psoriatic keratinocytes and is enhanced by EGFR signaling. Although IL-23 is also robustly induced by toll-like receptor agonists in dendritic cells and macrophages, IL-23 expression in these cell types is not regulated by TNFα, IL-17A, and EGFR signaling. Given that IL-23 is essential for maintaining Th17 activation, IL-23 induction by TNFα, IL-17A, and EGF in keratinocytes could play an important pathological role in psoriasis pathogenesis as well as the cutaneous rash associated with EGFR inhibition therapy.

Original languageEnglish (US)
Article number155357
JournalCytokine
DOIs
StateAccepted/In press - 2020

Keywords

  • Epidermal growth factor (EGF)
  • Interleukin 17A (IL-17A)
  • Keratinocytes
  • Psoriasis
  • Tumor necrosis factor alpha (TNFα)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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