Details

Autor(en) / Beteiligte

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

Titel

Inflammatory Skin Disease in K5.hTGF-[beta]1 Transgenic Mice Is Not Dependent on the IL-23/Th17 Inflammatory Pathway

Ist Teil von

• Journal of investigative dermatology, 2009-10, Vol.129 (10), p.2443

Ort / Verlag

London: Elsevier Limited

Erscheinungsjahr

2009

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.