Matches in SemOpenAlex for { <https://semopenalex.org/work/W4366184465> ?p ?o ?g. }
Showing items 1 to 83 of
83
with 100 items per page.
- W4366184465 endingPage "S202" @default.
- W4366184465 startingPage "S202" @default.
- W4366184465 abstract "Photosensitivity is a characteristic feature of some inflammatory skin diseases, including cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). Among the various hypotheses that explain this phenomenon, an aberrant sensitivity of keratinocytes (KC) deserves more attention, especially in the case of UVB photosensitivity, as the epidermis almost entirely absorbs UVB. However, the underlying mechanisms of UVB-induced KC death in an inflammatory milieu are unknown. Single-cell RNA sequencing on skin specimens from healthy volunteers and patients with CLE and DM showed a robust type-I-interferon (IFN-I) signature in basal KC, even in non-lesional skin, suggesting subclinical priming for subsequent inflammatory insults. ELISA on interstitial skin fluid from DM patients revealed elevated levels of IFN-beta. We, therefore, sought to investigate how IFN-Is affect KC death after UVB irradiation. Usingin vitroassays, we found pyroptosis, and not cell lysis, as the primary mechanism of UVB-induced inflammatory death in KCs, which was mediated through host-encoded pore-forming protein gasderminE (GSDME). Further, we discovered that GSDME cleavage happens in a caspase 3 (CASP3)-dependent manner. Using ZAK-alpha knockout KCs, we found a significant reduction in cleaved CASP3 and GSDME, suggesting ribotoxic stress as a mechanism of UVB-induced KC pyroptosis. Pretreatment of cultured KC with type I IFNs (IFN-alpha and beta) (p<0.0001) but not IFN-gamma enhanced GSDME-mediated pyroptosis and led to an increased release of interleukin-1 cytokine (p=0.01) following UVB exposure, which was blunted by pan-caspase inhibition. Bulk-RNA sequencing of KCs, we identified upregulation of apoptotic-related genes, including TXNIP, GCH1, and ATF3, after treatment with type I IFNs, suggesting them as targets that could prime KC sensitivity to UVB. These findings provide insight into the underlying mechanisms of UVB photosensitivity in IFN-I-mediated skin diseases." @default.
- W4366184465 created "2023-04-19" @default.
- W4366184465 creator A5001185791 @default.
- W4366184465 creator A5006953637 @default.
- W4366184465 creator A5024727052 @default.
- W4366184465 creator A5025552456 @default.
- W4366184465 creator A5051786747 @default.
- W4366184465 creator A5083133081 @default.
- W4366184465 creator A5086121144 @default.
- W4366184465 creator A5088921537 @default.
- W4366184465 date "2023-05-01" @default.
- W4366184465 modified "2023-10-03" @default.
- W4366184465 title "1178 Mechanisms of type I interferon-mediated UVB sensitivity in human keratinocytes" @default.
- W4366184465 doi "https://doi.org/10.1016/j.jid.2023.03.1191" @default.
- W4366184465 hasPublicationYear "2023" @default.
- W4366184465 type Work @default.
- W4366184465 citedByCount "0" @default.
- W4366184465 crossrefType "journal-article" @default.
- W4366184465 hasAuthorship W4366184465A5001185791 @default.
- W4366184465 hasAuthorship W4366184465A5006953637 @default.
- W4366184465 hasAuthorship W4366184465A5024727052 @default.
- W4366184465 hasAuthorship W4366184465A5025552456 @default.
- W4366184465 hasAuthorship W4366184465A5051786747 @default.
- W4366184465 hasAuthorship W4366184465A5083133081 @default.
- W4366184465 hasAuthorship W4366184465A5086121144 @default.
- W4366184465 hasAuthorship W4366184465A5088921537 @default.
- W4366184465 hasBestOaLocation W43661844651 @default.
- W4366184465 hasConcept C121332964 @default.
- W4366184465 hasConcept C139964883 @default.
- W4366184465 hasConcept C142724271 @default.
- W4366184465 hasConcept C153911025 @default.
- W4366184465 hasConcept C17172800 @default.
- W4366184465 hasConcept C185592680 @default.
- W4366184465 hasConcept C186807665 @default.
- W4366184465 hasConcept C190283241 @default.
- W4366184465 hasConcept C203014093 @default.
- W4366184465 hasConcept C2776914184 @default.
- W4366184465 hasConcept C2777209026 @default.
- W4366184465 hasConcept C2778690821 @default.
- W4366184465 hasConcept C2778751314 @default.
- W4366184465 hasConcept C31573885 @default.
- W4366184465 hasConcept C54355233 @default.
- W4366184465 hasConcept C62520636 @default.
- W4366184465 hasConcept C71924100 @default.
- W4366184465 hasConcept C86803240 @default.
- W4366184465 hasConceptScore W4366184465C121332964 @default.
- W4366184465 hasConceptScore W4366184465C139964883 @default.
- W4366184465 hasConceptScore W4366184465C142724271 @default.
- W4366184465 hasConceptScore W4366184465C153911025 @default.
- W4366184465 hasConceptScore W4366184465C17172800 @default.
- W4366184465 hasConceptScore W4366184465C185592680 @default.
- W4366184465 hasConceptScore W4366184465C186807665 @default.
- W4366184465 hasConceptScore W4366184465C190283241 @default.
- W4366184465 hasConceptScore W4366184465C203014093 @default.
- W4366184465 hasConceptScore W4366184465C2776914184 @default.
- W4366184465 hasConceptScore W4366184465C2777209026 @default.
- W4366184465 hasConceptScore W4366184465C2778690821 @default.
- W4366184465 hasConceptScore W4366184465C2778751314 @default.
- W4366184465 hasConceptScore W4366184465C31573885 @default.
- W4366184465 hasConceptScore W4366184465C54355233 @default.
- W4366184465 hasConceptScore W4366184465C62520636 @default.
- W4366184465 hasConceptScore W4366184465C71924100 @default.
- W4366184465 hasConceptScore W4366184465C86803240 @default.
- W4366184465 hasIssue "5" @default.
- W4366184465 hasLocation W43661844651 @default.
- W4366184465 hasOpenAccess W4366184465 @default.
- W4366184465 hasPrimaryLocation W43661844651 @default.
- W4366184465 hasRelatedWork W1548329668 @default.
- W4366184465 hasRelatedWork W2079864944 @default.
- W4366184465 hasRelatedWork W2102796637 @default.
- W4366184465 hasRelatedWork W2790206903 @default.
- W4366184465 hasRelatedWork W2937346106 @default.
- W4366184465 hasRelatedWork W2973533292 @default.
- W4366184465 hasRelatedWork W3000146621 @default.
- W4366184465 hasRelatedWork W3007266275 @default.
- W4366184465 hasRelatedWork W3207663138 @default.
- W4366184465 hasRelatedWork W4289886798 @default.
- W4366184465 hasVolume "143" @default.
- W4366184465 isParatext "false" @default.
- W4366184465 isRetracted "false" @default.
- W4366184465 workType "article" @default.