{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:52:05Z","timestamp":1791305525637,"version":"4.3.1"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["5 R01AI148430-05"],"award-info":[{"award-number":["5 R01AI148430-05"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Dartmouth College","award":["Dartmouth Cancer Center Prouty Grant"],"award-info":[{"award-number":["Dartmouth Cancer Center Prouty Grant"]}],"id":[{"id":"https:\/\/ror.org\/049s0rh22","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["R21AR079661-01"],"award-info":[{"award-number":["R21AR079661-01"]}],"id":[{"id":"https:\/\/ror.org\/006zn3t30","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Lupus Research Alliance","award":["Innovation Award"],"award-info":[{"award-number":["Innovation Award"]}],"id":[{"id":"https:\/\/ror.org\/02hkvsj16","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Congressionally Directed Medical Research Programs","award":["Lupus Research Program"],"award-info":[{"award-number":["Lupus Research Program"]}],"id":[{"id":"https:\/\/ror.org\/03g2zjp07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Congressionally Directed Medical Research Programs","award":["W81XWH-21-1-0889"],"award-info":[{"award-number":["W81XWH-21-1-0889"]}],"id":[{"id":"https:\/\/ror.org\/03g2zjp07","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Persistent production of type I interferons (IFN-Is) is a hallmark of cutaneous lupus erythematosus (CLE). Ultraviolet (UV) light stimulates IFN-I response in the skin and exacerbates CLE. Here, we identify V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) as a negative regulator of both basal and UV-induced IFN-I response in the skin and show that VISTA limits skin photosensitivity in an IFN-I-dependent manner, in part through Stimulator of Interferon Genes (STING). Furthermore, we demonstrate a novel role for VISTA in keratinocytes both at steady state and in response to UV light. Conditional deletion of VISTA in epidermal keratinocytes results in a ~10-fold increase in basal skin IFN-I scores and a heightened UV-induced skin injury score, both of which are dependent on IFN-I signaling. VISTA-targeting monoclonal antibodies suppress the UV-induced IFN-I response in human keratinocytes and in mice expressing human VISTA in vivo, thereby reducing UV-induced skin injury scores. Together, these findings identify VISTA as a keratinocyte-intrinsic checkpoint that restrains STING-associated IFN-I response in the skin and suggest VISTA agonism as a therapeutic strategy to limit photosensitivity in CLE.<\/jats:p>","DOI":"10.1172\/jci.insight.200540","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:00:59Z","timestamp":1791302459000},"source":"Crossref","is-referenced-by-count":0,"title":["Keratinocyte VISTA attenuates UV light-induced skin injury by suppressing cutaneous type I interferon (IFN-I) response"],"prefix":"10.1172","author":[{"given":"Zachary T.","family":"Peters","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay K.","family":"Mendyka","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J'Voughnn A.","family":"Blake","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu B.","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique N.","family":"Cortez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace E.","family":"Crossland","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicong","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0800-8007","authenticated-orcid":true,"given":"Myana","family":"Keusch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8505-4259","authenticated-orcid":true,"given":"Mrinal K.","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-0812","authenticated-orcid":true,"given":"Johann E.","family":"Gudjonsson","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea T.","family":"Barton","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9608-9841","authenticated-orcid":true,"given":"Bruce R.","family":"Blazar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler J.","family":"Curiel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodwell","family":"Mabaera","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria P.","family":"Werth","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kalus","sequence":"additional","affiliation":[{"name":"Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7340-6146","authenticated-orcid":true,"given":"Keith B.","family":"Elkon","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randolph J.","family":"Noelle","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6350-9582","authenticated-orcid":true,"given":"Sladjana","family":"Skopelja-Gardner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,6]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/200540\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:01:01Z","timestamp":1791302461000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/200540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.200540"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.200540","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]}}}