Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa.

Annals of the Rheumatic Diseases
Mrinal K SarkarJ Michelle Kahlenberg

Abstract

Skin inflammation and photosensitivity are common in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE), yet little is known about the mechanisms that regulate these traits. Here we investigate the role of interferon kappa (IFN-κ) in regulation of type I interferon (IFN) and photosensitive responses and examine its dysregulation in lupus skin. mRNA expression of type I IFN genes was analysed from microarray data of CLE lesions and healthy control skin. Similar expression in cultured primary keratinocytes, fibroblasts and endothelial cells was analysed via RNA-seq. IFNK knock-out (KO) keratinocytes were generated using CRISPR/Cas9. Keratinocytes stably overexpressing IFN-κ were created via G418 selection of transfected cells. IFN responses were assessed via phosphorylation of STAT1 and STAT2 and qRT-PCR for IFN-regulated genes. Ultraviolet B-mediated apoptosis was analysed via TUNEL staining. In vivo protein expression was assessed via immunofluorescent staining of normal and CLE lesional skin. IFNK is one of two type I IFNs significantly increased (1.5-fold change, false discovery rate (FDR) q<0.001) in lesional CLE skin. Gene ontology (GO) analysis showed that type I IFN responses were enr...Continue Reading

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Citations

Feb 13, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lam C TsoiJ Michelle Kahlenberg
Sep 27, 2019·Science Translational Medicine·Shuai ShaoJohann E Gudjonsson
Feb 16, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Katrin KleinFrank Stubenrauch
Mar 7, 2020·Current Opinion in Rheumatology·Hong ShiJ Michelle Kahlenberg
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