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

Shigetoshi Sano, Keith Syson Chan, Steve Carbajal, John Clifford, Mary Peavey, Kaoru Kiguchi, Satoshi Itami, Brian J. Nickoloff, John DiGiovanni

Research output: Contribution to journalArticlepeer-review

592 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)43-49
Number of pages7
JournalNature Medicine
Volume11
Issue number1
DOIs
StatePublished - Jan 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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