【摘 要】
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Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component gene
【机 构】
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McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Insti
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Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in y-secretase component genes.We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI.In this study,we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice.We determined that this mutant recapitulated the major phenotypes of AI,including hyperkeratosis of hair follicles and inflammation.In Ncstnflox/flox;K5-Cre mice,the IL-36a expression level markedly increased starting from postnatal day 0 (P0),and this increase occurred much earlier than those of TNF-α,IL-23A,IL-1 3,and TLR4.RNA-Seq analysis indicated that Sprr2d,a member of the small proline-rich protein 2 family,in the skin tissues of the Ncstnflox/flox,;K5-Cre mice was also upregulated on P0.Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression patte.Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and implicate malfunction of the skin barrier in the pathogenesis of AI.
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