The Tumor Necrosis Factor Superfamily Molecule LIGHT Promotes Keratinocyte Activity and Skin Fibrosis

The Journal of Investigative Dermatology
Rana HerroMichael Croft

Abstract

Several inflammatory diseases including scleroderma and atopic dermatitis display dermal thickening, epidermal hypertrophy, or excessive accumulation of collagen. Factors that might promote these features are of interest for clinical therapy. We previously reported that LIGHT, a TNF superfamily molecule, mediated collagen deposition in the lungs in response to allergen. We therefore tested whether LIGHT might similarly promote collagen accumulation and features of skin fibrosis. Strikingly, injection of recombinant soluble LIGHT into naive mice, either subcutaneously or systemically, promoted collagen deposition in the skin and dermal and epidermal thickening. This replicated the activity of bleomycin, an antibiotic that has been previously used in models of scleroderma in mice. Moreover skin fibrosis induced by bleomycin was dependent on endogenous LIGHT activity. The action of LIGHT in vivo was mediated via both of its receptors, HVEM and LTβR, and was dependent on the innate cytokine TSLP and TGF-β. Furthermore, we found that HVEM and LTβR were expressed on human epidermal keratinocytes and that LIGHT could directly promote TSLP expression in these cells. We reveal an unappreciated activity of LIGHT on keratinocytes and sugg...Continue Reading

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Citations

Jan 10, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Rana Herro, Michael Croft
Dec 5, 2015·Frontiers in Immunology·Emily HamsPadraic G Fallon
Mar 16, 2017·Nature Reviews. Gastroenterology & Hepatology·Xiaojun Jiang, Tom H Karlsen
May 23, 2017·Nature Communications·Daniel SidlerMichael Croft
Mar 10, 2017·Nature Reviews. Rheumatology·Michael Croft, Richard M Siegel
Aug 19, 2016·United European Gastroenterology Journal·Chao Li, John F Kuemmerle
Jan 18, 2018·The Journal of Experimental Medicine·Rana HerroMichael Croft
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Jun 21, 2017·Journal of Biomedical Science·Shie-Liang Hsieh, Wan-Wan Lin
Feb 6, 2017·Pharmaceutical Patent Analyst·Hermann Am Mucke
Apr 20, 2021·Multiple Sclerosis : Clinical and Laboratory Research·Yuan ZhouBruce Taylor
Jul 13, 2021·Frontiers in Immunology·Si-Hang Wang, Ya-Gang Zuo

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Methods Mentioned

BETA
transgenic

Software Mentioned

LSM
Pro Plus
Image
GraphPad Prism
Image Pro Analyser

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