{"@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/1362262945238759936.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1084/jem.20182192"}},{"identifier":{"@type":"URI","@value":"https://rupress.org/jem/article-pdf/216/4/867/1768598/jem_20182192.pdf"}}],"dc:title":[{"@value":"STING-mediated disruption of calcium homeostasis chronically activates ER stress and primes T cell death"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>STING gain-of-function mutations cause lung disease and T cell cytopenia through unknown mechanisms. Here, we found that these mutants induce chronic activation of ER stress and unfolded protein response (UPR), leading to T cell death by apoptosis in the StingN153S/+ mouse and in human T cells. Mechanistically, STING-N154S disrupts calcium homeostasis in T cells, thus intrinsically primes T cells to become hyperresponsive to T cell receptor signaling–induced ER stress and the UPR, leading to cell death. This intrinsic priming effect is mediated through a novel region of STING that we name “the UPR motif,” which is distinct from known domains required for type I IFN signaling. Pharmacological inhibition of ER stress prevented StingN153S/+ T cell death in vivo. By crossing StingN153S/+ to the OT-1 mouse, we fully restored CD8+ T cells and drastically ameliorated STING-associated lung disease. Together, our data uncover a critical IFN-independent function of STING that regulates calcium homeostasis, ER stress, and T cell survival.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382262945238759808","@type":"Researcher","foaf:name":[{"@value":"Jianjun Wu"}],"jpcoar:affiliationName":[{"@value":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 1"},{"@value":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 2"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262945238759812","@type":"Researcher","foaf:name":[{"@value":"Yu-Ju Chen"}],"jpcoar:affiliationName":[{"@value":"Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 3"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262945238759936","@type":"Researcher","foaf:name":[{"@value":"Nicole Dobbs"}],"jpcoar:affiliationName":[{"@value":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 1"},{"@value":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 2"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262945238759810","@type":"Researcher","foaf:name":[{"@value":"Tomomi Sakai"}],"jpcoar:affiliationName":[{"@value":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 1"},{"@value":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 2"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262945238759813","@type":"Researcher","foaf:name":[{"@value":"Jen Liou"}],"jpcoar:affiliationName":[{"@value":"Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 3"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262945238759809","@type":"Researcher","foaf:name":[{"@value":"Jonathan J. Miner"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 4"},{"@value":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 5"},{"@value":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 6"}]},{"@id":"https://cir.nii.ac.jp/crid/1382262945238759811","@type":"Researcher","foaf:name":[{"@value":"Nan Yan"}],"jpcoar:affiliationName":[{"@value":"Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 1"},{"@value":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 2"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00221007"},{"@type":"EISSN","@value":"15409538"}],"prism:publicationName":[{"@value":"Journal of Experimental Medicine"}],"dc:publisher":[{"@value":"Rockefeller University Press"}],"prism:publicationDate":"2019-03-18","prism:volume":"216","prism:number":"4","prism:startingPage":"867","prism:endingPage":"883"},"reviewed":"false","dc:rights":["http://www.rupress.org/terms/","https://creativecommons.org/licenses/by-nc-sa/4.0/"],"url":[{"@id":"https://rupress.org/jem/article-pdf/216/4/867/1768598/jem_20182192.pdf"}],"createdAt":"2019-03-18","modifiedAt":"2023-07-26","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360005516946914688","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"T Cell Co-stimulation and Functional Modulation by Innate Signals"}]},{"@id":"https://cir.nii.ac.jp/crid/1360306905165662208","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"ArfGAP2 promotes STING proton channel activity, cytokine transit, and autoinflammation"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1084/jem.20182192"},{"@type":"CROSSREF","@value":"10.1016/j.it.2020.01.003_references_DOI_V3IvSexKuSfyqUYCf5e4Fs96ute"},{"@type":"CROSSREF","@value":"10.1016/j.cell.2025.01.027_references_DOI_V3IvSexKuSfyqUYCf5e4Fs96ute"}]}