In:
Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-6-17)
Kurzfassung:
NLRP1 (NACHT and leucine-rich repeat-containing protein family, pyrin domain-containing protein 1) is an innate immune sensor that is involved in the formation of inflammasome complexes. NLRP1 hyperactivity has been reported to cause inherited autoinflammatory diseases including familial keratosis lichenoides chronica and NLRP1-associated autoinflammation with arthritis and dyskeratosis. We generated Nlrp1b (the mouse homologue of human NLRP1 ) gain-of-function knock-in ( Nlrp1b KI) mice with UVB irradiation-induced autoinflammatory skin lesions. We demonstrated that UVB irradiation induces IL-1β upregulation and IL-1β-dependent inflammation via caspase-1 activation in these Nlrp1b KI mice. RNA sequencing revealed the upregulation of inflammasome pathway-related genes, keratinocyte stress marker genes, and keratinocyte differentiation marker genes in the Nlrp1b KI mice after UVB irradiation. The skin inflammation and hyperkeratosis from UVB irradiation in the Nlrp1b KI mice were inhibited by both intraperitoneal and subcutaneous administration of anti-IL-1β antibodies before UVB irradiation. UVB irradiation and the IL-1β pathway are important in the pathogenesis of NLRP1-associated autoinflammatory skin lesions.
Materialart:
Online-Ressource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2022.876390
DOI:
10.3389/fimmu.2022.876390.s001
DOI:
10.3389/fimmu.2022.876390.s002
DOI:
10.3389/fimmu.2022.876390.s003
DOI:
10.3389/fimmu.2022.876390.s004
DOI:
10.3389/fimmu.2022.876390.s005
DOI:
10.3389/fimmu.2022.876390.s006
DOI:
10.3389/fimmu.2022.876390.s007
DOI:
10.3389/fimmu.2022.876390.s008
Sprache:
Unbekannt
Verlag:
Frontiers Media SA
Publikationsdatum:
2022
ZDB Id:
2606827-8
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