{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:26Z","timestamp":1792787606153,"version":"4.5.0"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":70,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82171005,82201093"],"award-info":[{"award-number":["82171005,82201093"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Rising Star Program","award":["22QA1405200"],"award-info":[{"award-number":["22QA1405200"]}]},{"name":"Shanghai Pujiang Program","award":["22PJ1409100"],"award-info":[{"award-number":["22PJ1409100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,16]]},"abstract":"<jats:p>\n                    Local immunoinflammatory events instruct skeletal stem cells (SSCs) to repair\/regenerate bone after injury, but mechanisms are incompletely understood. We hypothesized that specialized Tregs are necessary for bone repair and interact directly with SSCs through organ-specific messages. Both in human patients with bone fracture and a mouse model of bone injury, we identified a bone injury\u2013responding Treg subpopulation with bone-repair capacity marked by CCR8. Local production of CCL1 induced a massive migration of CCR8\n                    <jats:sup>+<\/jats:sup>\n                    Tregs from periphery to the injury site. Depending on secretion of progranulin (PGRN), a protein encoded by the granulin (\n                    <jats:italic>Grn<\/jats:italic>\n                    ) gene, CCR8\n                    <jats:sup>+<\/jats:sup>\n                    Tregs supported the accumulation and osteogenic differentiation of SSCs and thereby bone repair. Mechanistically, we revealed that CCL1 enhanced expression levels of basic leucine zipper ATF-like transcription factor (BATF) in CCR8\n                    <jats:sup>+<\/jats:sup>\n                    Tregs, which bound to the\n                    <jats:italic>Grn<\/jats:italic>\n                    promoter and increased\n                    <jats:italic>Grn<\/jats:italic>\n                    translational output and then PGRN secretion. Together, our work provides a new perspective in osteoimmunology and highlights possible ways of manipulating Treg signaling to enhance bone repair and regeneration.\n                  <\/jats:p>","DOI":"10.1172\/jci180679","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T12:56:13Z","timestamp":1730984173000},"source":"Crossref","is-referenced-by-count":37,"title":["Progranulin-dependent repair function of regulatory T cells drives bone-fracture healing"],"prefix":"10.1172","volume":"135","author":[{"given":"Ruiying","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 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Shanghai, China."},{"name":"Department of Integrated TCM & Western Medicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China."},{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China."},{"name":"Department of Oncology, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio S.","family":"Tonetti","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 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