Inflammatory skin disease in K5.hTGF-Β1 transgenic mice is not dependent on the IL-23/Th17 inflammatory pathway

Erin L. Fitch, Heather L. Rizzo, Stephen E. Kurtz, Keith W. Wegmann, Wei Gao, Jacqueline M. Benson, David J. Hinrichs, Andrew Blauvelt

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


In the presence of IL-6, transforming growth factor (TGF)-Β1 induces differentiation of T helper (Th) 17 cells in mice. Interleukin (IL)-23, a heterodimeric cytokine composed of IL-23p19 and IL-12/23p40 subunits, stimulates the growth and expansion of Th17 cells, and has been implicated in psoriasis pathogenesis. To study the associations between TGF-Β1, the IL-23/Th17 inflammatory pathway, and psoriasis, we investigated inflammatory skin disease in transgenic mice that constitutively overexpress human TGF-Β1 in basal keratinocytes (K5.hTGF-Β1 transgenic mice); these mice had previously been reported as having a psoriasis-like disease. K5.hTGF-Β1 transgenic mice had high levels of TGF-Β1 mRNA and protein in both skin and serum. Levels of cytokines involved in IL-23/Th17-mediated inflammation were not elevated in lesional skin compared with those in non-lesional and wild-type skin. It is noteworthy that IL-4 and IgE were markedly elevated in inflamed skin and serum, respectively, of transgenic mice. Monoclonal antibodies (mAbs) specifically directed against IL-23p19 or IL-12/23p40 had no clinical effect on established inflammatory skin disease in K5.hTGF-Β1 transgenic mice, whereas the same mAbs were able to block the development of murine experimental autoimmune encephalomyelitis, an IL-23/Th17-mediated disease. In summary, the IL-23/Th17 inflammatory pathway is not responsible for the maintenance of inflammatory skin disease in K5.hTGF-Β1 transgenic mice.

Original languageEnglish (US)
Pages (from-to)2443-2450
Number of pages8
JournalJournal of Investigative Dermatology
Issue number10
StatePublished - Oct 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


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