Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model.
Here we report that epidermal keratinocytes in psoriatic lesions are characterized by activated Stat3. Transgenic mice with keratinocytes expressing a constitutively active Stat3 (K5.Stat3C mice) develop a skin phenotype either spontaneously, or in response to wounding, that closely resembles psoriasis. Keratinocytes from K5.Stat3C mice show upregulation of several molecules linked to the pathogenesis of psoriasis. In addition, the development of psoriatic lesions in K5.Stat3C mice requires cooperation between Stat3 activation in keratinocytes and activated T cells. Finally, abrogation of Stat3 function by a decoy oligonucleotide inhibits the onset and reverses established psoriatic lesions in K5.Stat3C mice. Thus, targeting Stat3 may be potentially therapeutic in the treatment of psoriasis.
Sano
Shigetoshi
S
Department of Carcinogenesis, University of Texas, M. D. Anderson Cancer Center, Science Park - Research Division, 1808 Park Road 1C, PO Box 389, Smithville, Texas 78957, USA. ssano@mdanderson.org
Chan
Keith Syson
KS
Carbajal
Steve
S
Clifford
John
J
Peavey
Mary
M
Kiguchi
Kaoru
K
Itami
Satoshi
S
Nickoloff
Brian J
BJ
DiGiovanni
John
J
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011565:Psoriasis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D016511:Severe Combined Immunodeficiency / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators