{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:32:25Z","timestamp":1790836345186,"version":"4.1.0"},"reference-count":37,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":35,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["AI128358"],"award-info":[{"award-number":["AI128358"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012051","name":"Lupus Research Alliance","doi-asserted-by":"crossref","award":["Innovation Award"],"award-info":[{"award-number":["Innovation Award"]}],"id":[{"id":"10.13039\/100012051","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL154674"],"award-info":[{"award-number":["HL154674"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["GM107000"],"award-info":[{"award-number":["GM107000"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["AI132152"],"award-info":[{"award-number":["AI132152"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["AI178978"],"award-info":[{"award-number":["AI178978"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL165787"],"award-info":[{"award-number":["HL165787"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Henry Gustav Floren Trust","award":["Henry Gustav Floren Trust"],"award-info":[{"award-number":["Henry Gustav Floren Trust"]}]},{"name":"Stanford Department of Medicine","award":["Team Science Program"],"award-info":[{"award-number":["Team Science Program"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,22]]},"abstract":"<jats:p>Gain-of-function mutations in the dsDNA sensing adaptor STING lead to a severe autoinflammatory syndrome known as STING-associated vasculopathy with onset in infancy (SAVI). Patients with SAVI develop interstitial lung disease (ILD) and produce autoantibodies that are commonly associated with systemic autoimmune diseases. Mice expressing the most common SAVI mutation, STING V154M (VM), similarly develop ILD but exhibit severe T and B cell lymphopenia and low serum Ig titers, and they lack autoantibodies. Importantly, lethally irradiated VM hosts reconstituted with WT stem cells (WT\u2192VM) still develop ILD. In this study, we find that WT\u2192VM chimeras had restored B cell function, produced autoantibodies, and thereby recapitulated the loss of tolerance seen in patients with SAVI. Lymphocytes derived from both WT and BCR or TCR transgenic (Tg) donors accumulated in the extravascular lung tissue of WT+Tg\u2192VM mixed chimeras, but lymphocyte activation and germinal center formation required WT cells with a diverse repertoire. Furthermore, when T cells isolated from the WT\u2192VM chimeras were adoptively transferred to naive Rag1-deficient secondary hosts, they trafficked to the lung and recruited neutrophils. Overall, these findings indicated that VM expression by radioresistant cells promoted the activation of autoreactive B cells and T cells that then differentiated into potentially pathogenic effector subsets.<\/jats:p>","DOI":"10.1172\/jci.insight.174331","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T12:01:09Z","timestamp":1721304069000},"source":"Crossref","is-referenced-by-count":4,"title":["Activation of autoreactive lymphocytes in the lung by radioresistant cells expressing a STING gain-of-function mutation"],"prefix":"10.1172","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5855-1006","authenticated-orcid":true,"given":"Kevin MingJie","family":"Gao","sequence":"first","affiliation":[{"name":"Division of Innate Immunity and"},{"name":"Division of Rheumatology, Department of Medicine, UMass Chan Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy","family":"Chiang","sequence":"additional","affiliation":[{"name":"Division of Innate Immunity and"},{"name":"Division of Rheumatology, Department of Medicine, UMass Chan Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Division of Innate Immunity and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1861-1147","authenticated-orcid":true,"given":"Xihui","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1181-1565","authenticated-orcid":true,"given":"Paul J.","family":"Utz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4329-9607","authenticated-orcid":true,"given":"Kerstin","family":"N\u00fcndel","sequence":"additional","affiliation":[{"name":"Division of Innate Immunity and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3175-609X","authenticated-orcid":true,"given":"Kate A.","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, UMass Chan Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Marshak-Rothstein","sequence":"additional","affiliation":[{"name":"Division of Innate Immunity and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.40"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-00544-4"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20161596"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-016-1465-5"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.11.007"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818281116"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171351"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.04.034"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20182192"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.009"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701405"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1312625"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2202327119"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818281116"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055531"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151722"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28756"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000028"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04248-x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.11.018"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.032"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/art.41090"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114114"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2018.1411190"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00009113"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201510-2102LE"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.3.1184"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.05.008"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-023-01595-4"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2022.05.025"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.005"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402425"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1917-7"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900499"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.026"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1186\/ar2771"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2021-221926"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/174331\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:40:48Z","timestamp":1779136848000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/174331"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,18]]},"references-count":37,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,7,18]]},"published-print":{"date-parts":[[2024,8,22]]}},"alternative-id":["10.1172\/jci.insight.174331"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.174331","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,18]]},"article-number":"e174331"}}