{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:23:44Z","timestamp":1792023824726,"version":"4.4.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":73,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Defense Scleroderma Research Program Translational Research Partnership Award","award":["SL200016P1"],"award-info":[{"award-number":["SL200016P1"]}]},{"DOI":"10.13039\/100000069","name":"NIAMS","doi-asserted-by":"crossref","award":["NIH P30-AR-070253"],"award-info":[{"award-number":["NIH P30-AR-070253"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>\n                    Interstitial lung disease (ILD) is a major cause of morbidity and mortality in systemic sclerosis (SSc); however, the immunopathologic mechanisms driving lung disease in SSc are unclear. T cells have been implicated as a likely driver of lung injury in SSc. Here, we evaluated T cells in the blood of patients with SSc-ILD and identified a specific population of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells that was expanded in patients with SSc-ILD. Cytotoxic effector memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells marked by CD57 expression were preferentially expanded in patients with SSc-ILD compared with patients with SSc but no ILD and control individuals and showed prominent clonal expansion. These CD57\n                    <jats:sup>+<\/jats:sup>\n                    T effector memory (Tem) cells differed from T effector memory cells reexpressing CD45RA (Temra) transcriptomically and functionally, with cytotoxic function that was enhanced by CD155 engagement of the costimulatory receptor CD226. We performed immunostaining of lung tissue samples obtained from independent patients with SSc-ILD (biopsy or explant) and confirmed the presence of CD57\n                    <jats:sup>+<\/jats:sup>\n                    Tem cells. In parallel, we analyzed publicly available lung scRNA-seq datasets from multiple ILD cohorts and identified endothelial cells as a likely source of CD155 for the activation of CD57\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T cells. Together, the results implicate a CD57\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell population as a potential mediator of lung injury in SSc-ILD.\n                  <\/jats:p>","DOI":"10.1172\/jci194288","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T18:19:08Z","timestamp":1771352348000},"source":"Crossref","is-referenced-by-count":2,"title":["A CD57+CD8+ T cell subset links T cell cytotoxicity to fibrotic lung disease in systemic sclerosis"],"prefix":"10.1172","volume":"136","author":[{"given":"Takanori","family":"Sasaki","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Sowerby","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Higashioka","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryne E.","family":"Marks","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehreen","family":"Elahee","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, BWH and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Dellaripa","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women\u2019s Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard I.","family":"Ainsworth","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology, and"},{"name":"Kao Autoimmunity Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly E.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-7501","authenticated-orcid":true,"given":"Nunzio","family":"Bottini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology, and"},{"name":"Kao Autoimmunity Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3108-6164","authenticated-orcid":true,"given":"Paul","family":"Wolters","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Allergy and Sleep, Department of Medicine, UCSF, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9095-3109","authenticated-orcid":true,"given":"Edy Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, BWH and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Boin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology, 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