Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model
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.
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STAT3 activation seems to be protective against UV.
“STAT3 activation seems to be protective (Shen et al., 2001; Chan et al., 2004b; Sano et al., 2005; Aziz et al., 2007a; Barry et al., 2010; Bito et al., 2010a,b).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Sano et al., 2005
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Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth
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IκBζ is a key driver in the development of psoriasis
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Inflammation and Cancer: Is the Link as Simple as We Think?
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- Authors
- Sano, S., Chan, K. S., Carbajal, S., Clifford, J., Peavey, M., Kiguchi, K., Itami, S., Nickoloff, B. J., & DiGiovanni, J.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Louisiana State University (US)
- The University of Osaka (JP)
- Loyola University Chicago (US)
- Corresponding author
- Sano, Shigetoshi
- DiGiovanni, John
- ORCID
- Venue
- Nature Medicine
- Published
- 2004-12-12
- Volume
- 11
- Issue
- 1
- Pages
- 43-49
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2074360288
- Cited by
- 752
- References
- 2
- Citations by year
- 2026: 24 · 2025: 29 · 2024: 35 · 2023: 30 · 2022: 40 · 2021: 37 · 2020: 33 · 2019: 36 · 2018: 29 · 2017: 38 · 2016: 32 · 2015: 28 · 2014: 27 · 2013: 32 · 2012: 40
- FWCI
- 15.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA-16672, CA76520, R01CA076520, P30CA016672)
- National Institute of Environmental Health Sciences (#ES07784, U01 ES11047, P30ES007784, U01ES011047)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-40065, R01AR040065)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- STAT3, psoriasis, keratinocytes, transgenic mouse model, T cell activation, skin inflammation, decoy oligonucleotides
- MeSH terms
- Animals, Disease Models, Animal, DNA-Binding Proteins, Epidermis, Humans, Mice, Transgenic, Psoriasis, T-Lymphocytes, Transplantation, Heterologous, Signal Transduction, Trans-Activators, Keratinocytes, Skin Transplantation, Severe Combined Immunodeficiency, STAT3 Transcription Factor, Mice
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