{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361981469901946752.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1084/jem.20082242"}},{"identifier":{"@type":"URI","@value":"https://rupress.org/jem/article-pdf/206/5/1135/1901522/jem_20082242.pdf"}}],"dc:title":[{"@value":"Kallikrein 5 induces atopic dermatitis–like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Netherton syndrome (NS) is a severe genetic skin disease with constant atopic manifestations that is caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lymphoepithelial Kazal-type–related inhibitor (LEKTI). Lack of LEKTI causes stratum corneum detachment secondary to epidermal proteases hyperactivity. This skin barrier defect favors allergen absorption and is generally regarded as the underlying cause for atopy in NS. We show for the first time that the pro-Th2 cytokine thymic stromal lymphopoietin (TSLP), the thymus and activation-regulated chemokine, and the macrophage-derived chemokine are overexpressed in LEKTI-deficient epidermis. This is part of an original biological cascade in which unregulated kallikrein (KLK) 5 directly activates proteinase-activated receptor 2 and induces nuclear factor κB–mediated overexpression of TSLP, intercellular adhesion molecule 1, tumor necrosis factor α, and IL8. This proinflammatory and proallergic pathway is independent of the primary epithelial failure and is activated under basal conditions in NS keratinocytes. This cell-autonomous process is already established in the epidermis of Spink5−/− embryos, and the resulting proinflammatory microenvironment leads to eosinophilic and mast cell infiltration in a skin graft model in nude mice. Collectively, these data establish that uncontrolled KLK5 activity in NS epidermis can trigger atopic dermatitis (AD)–like lesions, independently of the environment and the adaptive immune system. They illustrate the crucial role of protease signaling in skin inflammation and point to new therapeutic targets for NS as well as candidate genes for AD and atopy.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381981469901946752","@type":"Researcher","foaf:name":[{"@value":"Anaïs Briot"}],"jpcoar:affiliationName":[{"@value":"Institut National de la Santé et de la Recherche Médicale, U563, Toulouse F-31300, France 1"},{"@value":"Université Toulouse III Paul-Sabatier, Toulouse F-31400, France 2"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981469901946757","@type":"Researcher","foaf:name":[{"@value":"Céline Deraison"}],"jpcoar:affiliationName":[{"@value":"Institut National de la Santé et de la Recherche Médicale, U563, Toulouse F-31300, France 1"},{"@value":"Université Toulouse III Paul-Sabatier, Toulouse F-31400, France 2"},{"@value":"Departement de Génétique Médicale, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Toulouse F31000, France 3"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981469901946753","@type":"Researcher","foaf:name":[{"@value":"Matthieu Lacroix"}],"jpcoar:affiliationName":[{"@value":"Institut National de la Santé et de la Recherche Médicale, U563, Toulouse F-31300, France 1"},{"@value":"Université Toulouse III Paul-Sabatier, Toulouse F-31400, France 2"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981469901946754","@type":"Researcher","foaf:name":[{"@value":"Chrystelle Bonnart"}],"jpcoar:affiliationName":[{"@value":"Institut National de la Santé et de la Recherche Médicale, U563, Toulouse F-31300, France 1"},{"@value":"Université Toulouse III Paul-Sabatier, Toulouse F-31400, France 2"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981469901946755","@type":"Researcher","foaf:name":[{"@value":"Aurélie Robin"}],"jpcoar:affiliationName":[{"@value":"Institut National de la Santé et de la Recherche Médicale, U563, Toulouse F-31300, France 1"},{"@value":"Université Toulouse III Paul-Sabatier, Toulouse F-31400, France 2"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981469901946624","@type":"Researcher","foaf:name":[{"@value":"Céline Besson"}],"jpcoar:affiliationName":[{"@value":"Institut National de la Santé et de la Recherche Médicale, U563, Toulouse F-31300, France 1"},{"@value":"Université Toulouse III Paul-Sabatier, Toulouse F-31400, France 2"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981469901946758","@type":"Researcher","foaf:name":[{"@value":"Pierre Dubus"}],"jpcoar:affiliationName":[{"@value":"EA2406 Université Bordeaux 2 Victor Segalen, Bordeaux F-33076, France 4"}]},{"@id":"https://cir.nii.ac.jp/crid/1381981469901946756","@type":"Researcher","foaf:name":[{"@value":"Alain Hovnanian"}],"jpcoar:affiliationName":[{"@value":"Institut National de la Santé et de la Recherche Médicale, U563, Toulouse F-31300, France 1"},{"@value":"Université Toulouse III Paul-Sabatier, Toulouse F-31400, France 2"},{"@value":"Departement de Génétique Médicale, Hôpital Purpan, Centre Hospitalier Universitaire de Toulouse, Toulouse F31000, France 3"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"15409538"},{"@type":"PISSN","@value":"00221007"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/00221007"}],"prism:publicationName":[{"@value":"Journal of Experimental Medicine"}],"dc:publisher":[{"@value":"Rockefeller University Press"}],"prism:publicationDate":"2009-05-04","prism:volume":"206","prism:number":"5","prism:startingPage":"1135","prism:endingPage":"1147"},"reviewed":"false","url":[{"@id":"https://rupress.org/jem/article-pdf/206/5/1135/1901522/jem_20082242.pdf"}],"createdAt":"2009-05-04","modifiedAt":"2024-03-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002217145045760","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Kallikrein-related Peptidase 5 Functions in Proteolytic Processing of Profilaggrin in Cultured Human 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dermatitis"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204474558336","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"経皮感作と喘息"},{"@language":"en","@value":"Epicutaneous sensitization and asthma"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204631146368","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"New Insights into Atopic Dermatitis: Role of Skin Barrier and Immune Dysregulation"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204631981824","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Cellular and Molecular Mechanisms of TSLP Function in Human Allergic Disorders - TSLP Programs the \"Th2 code\" in Dendritic Cells"},{"@value":"Cellular and molecular mechanisms of TSLP function in human allergic disorders— TSLP programs the \"Th2 code\" in dendritic cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204631984640","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"TSLP Expression: Cellular Sources, Triggers, and Regulatory Mechanisms"},{"@value":"TSLP expression: cellular sources, triggers, and regulatory mechamisms"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204633811328","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Barrier Dysfunction Caused by Environmental Proteases in the Pathogenesis of Allergic Diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204650175872","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Natural history of Atopic dermatitis-Outside-Inside-Outside Story-"},{"@language":"ja","@value":"自然史からみたアトピー性皮膚炎の考え方　―Ｏｕｔｓｉｄｅ―Ｉｎｓｉｄｅ―Ｏｕｔｓｉｄｅストーリー―"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204875483776","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Th2 cytokines increase kallikrein 7 expression and function in patients with atopic dermatitis"},{"@language":"ja","@value":"Th２サイトカインはアトピー性皮膚炎患者におけるカリクレイン７の発現と機能を増強する"},{"@value":"平成24年度岡山医学会賞 総合研究奨励賞(結城賞) Th2サイトカインはアトピー性皮膚炎患者におけるカリクレイン7の発現と機能を増強する"},{"@language":"ja-Kana","@value":"ヘイセイ 24ネンド オカヤマ イガッカイショウ ソウゴウ ケンキュウ ショウレイショウ(ユウキショウ) Th2 サイトカイン ワ アトピーセイ ヒフエン カンジャ ニ オケル カリクレイン 7 ノ ハツゲン ト キノウ オ ゾウキョウ スル"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001205180870272","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Exacerbation of Allergic Diseases by Chemicals: Role of TSLP"},{"@value":"Current Perspective : Exacerbation of Allergic Diseases by Chemicals : Role of TSLP"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679279369984","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Corstruction and Impairment of Skin Barrier Functions Originated from Keratinocytes"},{"@language":"ja","@value":"表皮角化細胞が担う皮膚バリア機能とその障害メカニズム"},{"@language":"ja-Kana","@value":"ヒョウヒ カクカ サイボウ ガ ニナウ ヒフ バリア キノウ ト ソノ ショウガイ メカニズム"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679608548224","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Food allergy preceded by contact urticaria due to the same food: Involvement of epicutaneous sensitization in food allergy"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679608692480","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Mouse Models of 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