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Nature Medicine 11, 43 - 49 (2004)
Published online: 12 December 2004 | doi:10.1038/nm1162

Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model

Shigetoshi Sano1,5,6, Keith Syson Chan1,5, Steve Carbajal1, John Clifford2, Mary Peavey1, Kaoru Kiguchi1, Satoshi Itami3, Brian J Nickoloff4 & John DiGiovanni1


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.


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