UVB-Induced Skin Autoinflammation Due to Nlrp1b Mutation and Its Inhibition by Anti-IL-1β Antibody

Frontiers in Immunology

Yoshinao Muro¹  Masashi Akiyama¹  Yuya Murase¹  Takuya Takeichi¹  Tamio Ohno²  Yuki Miyasaka²  Jun Koseki³  Teppei Shimamura³ 

[1] Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan;Division of Experimental Animals, Nagoya University Graduate School of Medicine, Nagoya, Japan;Division of Systems Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan;

关键词: NLRP1;    NLRP1B;    inflammasome;    UVB;    IL-1β;    IL-18;   

DOI  :  10.3389/fimmu.2022.876390

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown