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Article
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

1  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.

2  Department of Biochemistry and Molecular Biology, Louisiana State University, Health Sciences Center, School of Medicine in Shreveport and Feist-Weiller Cancer Center, 1501 Kings Highway, Shreveport, Louisiana 71130, USA.

3  Department of Dermatology, Osaka University Graduate School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

4  Department of Pathology and Department of Microbiology and Immunology, Loyola University of Chicago, Cardinal Bernardin Cancer Center, 2160 South First Avenue, Room 301, Maywood, Illinois 60153-5385, USA.

5  These authors contributed equally to this work.

6  Permanent address: Department of Dermatology, Osaka University Graduate School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Correspondence should be addressed to John DiGiovanni jdigiovanni@sprd1.mdacc.tmc.edu or Shigetoshi Sano ssano@mdanderson.org
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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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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