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

11 Scopus citations


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
StatePublished - Feb 2021
Externally publishedYes


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

ASJC Scopus subject areas

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


Dive into the research topics of 'Synergistic induction of IL-23 by TNFα, IL-17A, and EGF in keratinocytes'. Together they form a unique fingerprint.

Cite this