Inflammatory skin disease in K5.hTGF-beta1 transgenic mice is not dependent on the IL-23/Th17 inflammatory pathway

J Invest Dermatol. 2009 Oct;129(10):2443-50. doi: 10.1038/jid.2009.88. Epub 2009 Apr 9.


In the presence of IL-6, transforming growth factor (TGF)-beta1 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-beta1, the IL-23/Th17 inflammatory pathway, and psoriasis, we investigated inflammatory skin disease in transgenic mice that constitutively overexpress human TGF-beta1 in basal keratinocytes (K5.hTGF-beta1 transgenic mice); these mice had previously been reported as having a psoriasis-like disease. K5.hTGF-beta1 transgenic mice had high levels of TGF-beta1 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-beta1 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-beta1 transgenic mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Cells, Cultured
  • Disease Models, Animal
  • Immunoglobulin E / metabolism
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Interleukin-17 / metabolism*
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism*
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Transgenic
  • Psoriasis / etiology
  • Psoriasis / metabolism*
  • Psoriasis / pathology
  • RNA, Messenger / metabolism
  • Signal Transduction / physiology*
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • T-Lymphocytes, Helper-Inducer / pathology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*


  • Antibodies, Monoclonal
  • Interleukin-17
  • Interleukin-23
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Interleukin-12
  • Interleukin-4
  • Immunoglobulin E