Inflammatory skin disease in K5.hTGF-beta1 transgenic mice is not dependent on the IL-23/Th17 inflammatory pathway.
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.
Department of Dermatology, Oregon Health & Science University, Portland, Oregon 97239, USA.
Erin L
EL
Fitch
Heather L
HL
Rizzo
Stephen E
SE
Kurtz
Keith W
KW
Wegmann
Wei
W
Gao
Jacqueline M
JM
Benson
David J
DJ
Hinrichs
Andrew
A
Blauvelt
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011565:Psoriasis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D020381:Interleukin-17; D053759:Interleukin-23; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E