{"@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/1362262943473382272.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/s41598-018-25282-2"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41598-018-25282-2.pdf"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41598-018-25282-2"}}],"dc:title":[{"@value":"The psoriasis-protective TYK2 I684S variant impairs IL-12 stimulated pSTAT4 response in skin-homing CD4+ and CD8+ memory T-cells"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>Tyrosine kinase 2 (TYK2) belongs to the Janus kinase (JAK) family of tyrosine kinases, which transmit signals from activated cytokine receptors. GWAS have consistently implicated <jats:italic>TYK2</jats:italic> in psoriasis susceptibility. We performed an in-depth association analysis of <jats:italic>TYK2</jats:italic> using GWAS and resequencing data. Strong genetic association of three nonsynonymous variants in the exonic regions of the <jats:italic>TYK2</jats:italic> gene (rs34536443, rs12720356, and rs2304256) were found. rs12720356 encoding I684S is predicted to be deleterious based on its location in the pseudokinase domain. We analyzed PBMCs from 29 individuals representing the haplotypes containing each of the significantly associated signals. STAT4 phosphorylation was evaluated by phospho-flow cytometry after CD3/CD28 activation of cells followed by IL-12 stimulation. Individuals carrying the protective I684S variant manifested significantly reduced p-STAT4 levels in CD4 + CD25 + CD45RO+ (mean Stimulation Index (S.I.) 48.08, n = 10) and CD8 + CD25 + CD45RO + cells (S.I. 55.71, n = 10), compared to controls homozygous for the ancestral haplotype (S.I. 68.19, n = 10 (p = 0.002) and 76.76 n = 10 (p = 0.0008) respectively). Reduced p-STAT4 levels were also observed in skin-homing, cutaneous lymphocyte associated antigen (CLA)-positive CD4 and CD8 cells from I684S carriers. No significant changes in p-STAT4 for the psoriasis-associated variant rs34536443 was found. These data establish the functional significance of the <jats:italic>TYK2</jats:italic> I684S variant in psoriasis susceptibility.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382262943473382277","@type":"Researcher","foaf:name":[{"@value":"C. Enerbäck"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943473382279","@type":"Researcher","foaf:name":[{"@value":"C. Sandin"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943473382272","@type":"Researcher","foaf:name":[{"@value":"S. Lambert"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943473382280","@type":"Researcher","foaf:name":[{"@value":"M. Zawistowski"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943473382278","@type":"Researcher","foaf:name":[{"@value":"P. E. Stuart"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943473382273","@type":"Researcher","foaf:name":[{"@value":"D. Verma"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943473382275","@type":"Researcher","foaf:name":[{"@value":"L. C. Tsoi"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943473382276","@type":"Researcher","foaf:name":[{"@value":"R. P. Nair"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943473382281","@type":"Researcher","foaf:name":[{"@value":"A. Johnston"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262943473382274","@type":"Researcher","foaf:name":[{"@value":"J. T. Elder"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20452322"}],"prism:publicationName":[{"@value":"Scientific Reports"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2018-05-04","prism:volume":"8","prism:number":"1","prism:startingPage":"7043"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by/4.0","https://creativecommons.org/licenses/by/4.0"],"url":[{"@id":"https://www.nature.com/articles/s41598-018-25282-2.pdf"},{"@id":"https://www.nature.com/articles/s41598-018-25282-2"}],"createdAt":"2018-04-30","modifiedAt":"2022-12-21","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360572092628034688","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Genetic Susceptibility of the Host in Virus-Induced Diabetes"}]},{"@id":"https://cir.nii.ac.jp/crid/1361975845889831936","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Identification of rare coding variants in TYK2 protective for rheumatoid arthritis in the Japanese population and their effects on cytokine signalling"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1038/s41598-018-25282-2"},{"@type":"CROSSREF","@value":"10.3390/microorganisms8081133_references_DOI_Wc2JDV8gBn8aDU5FS0oo4NA7ay0"},{"@type":"CROSSREF","@value":"10.1136/annrheumdis-2019-215062_references_DOI_Wc2JDV8gBn8aDU5FS0oo4NA7ay0"}]}