{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:54:45Z","timestamp":1789412085432,"version":"build-2803163510"},"reference-count":42,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"unspecified","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0908200"],"award-info":[{"award-number":["2020YFA0908200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Trials from Nanjing Drum Tower Hospital","award":["2022-YXZX-MY-03"],"award-info":[{"award-number":["2022-YXZX-MY-03"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572069"],"award-info":[{"award-number":["82572069"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20231119"],"award-info":[{"award-number":["BK20231119"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20243061"],"award-info":[{"award-number":["BK20243061"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Program of Jiangsu Provincial Health and Wellness Commission","award":["H2023087"],"award-info":[{"award-number":["H2023087"]}]},{"DOI":"10.13039\/100016966","name":"Bethune Charitable Foundation","doi-asserted-by":"publisher","award":["BCF-QYWL-FS-2024-3"],"award-info":[{"award-number":["BCF-QYWL-FS-2024-3"]}],"id":[{"id":"10.13039\/100016966","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,12,16]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterised by progressive pulmonary fibrosis. This study aimed to investigate the role of programmed death-1 (PD-1)-expressing T cells in SSc-ILD pathogenesis and evaluate the therapeutic potential and mechanism of mesenchymal stromal cells (MSCs) in mitigating fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PD-1 expression in T cells from 30 patients with SSc (including SSc-ILD and SSc-non-ILD (nILD) subgroups) and 15 healthy controls (HCs) was analysed via flow cytometry. A bleomycin (BLM)-induced SSc-ILD mouse model was established to evaluate the effects of MSCs in the treatment of lung collagen deposition and inflammation in SSc-ILD. MSCs were administered intravenously to BLM-treated mice, with programmed death-ligand 1 (PD-L1) knockdown (using small interfering RNA targeting PD-L1, siPD-L1) used to explore the mechanism of MSCs on PD-1\/PD-L1 pathway. The effects of MSCs on CD4\n                      <jats:sup>+<\/jats:sup>\n                      PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T cell proliferation and apoptosis were evaluated by in vitro co-culture experiment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PD-1 expression was significantly elevated in CD3\n                      <jats:sup>+<\/jats:sup>\n                      and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells of patients with SSc-ILD compared with HCs and SSc-nILD subgroups. In BLM-induced mice, CD4\n                      <jats:sup>+<\/jats:sup>\n                      PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T cells in the lung tissues increased progressively, which was correlated with the severity of lung fibrosis. CD4\n                      <jats:sup>+<\/jats:sup>\n                      PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T cells directly stimulated fibroblasts to upregulate the expression of collagen and transforming growth factor \u03b21. Treatment with MSCs reduced pulmonary inflammation, fibrosis and PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T cell frequencies in lung tissues of BLM-induced mice. This therapeutic effect was PD-L1-dependent, as it was mediated by the MSC-induced suppression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T cells drive fibrosis in SSc-ILD, and MSCs ameliorate disease by suppressing PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T cells through PD-L1-mediated mechanisms. These findings highlight PD-1 as a therapeutic target and support the clinical investigation of MSC-based interventions for SSc-ILD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-006324","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T15:31:34Z","timestamp":1767713494000},"page":"e006324","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Mesenchymal stromal cells ameliorate systemic sclerosis-interstitial lung disease via PD-1\/PD-L1 signalling axis"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4825-308X","authenticated-orcid":false,"given":"Yuxuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, 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