{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:10:30Z","timestamp":1785849030248,"version":"3.56.0"},"reference-count":70,"publisher":"Wiley","issue":"34","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Inflammation is a hallmark of intervertebral disc degeneration (IVDD) characterized by immune cell infiltration and cytokine secretion. Stage\u2010specific transcriptomic analyses of IVDD via single\u2010cell RNA sequencing (scRNA\u2010seq) have primarily focused on nucleus pulposus cell phenotypes but not immune subpopulations. In other disease contexts, integrating genome\u2010wide association studies (GWAS) with scRNA\u2010seq data has provided insights on pathomechanisms in relation to specific cellular subpopulations via single\u2010cell disease relevance scores (scDRS). However, such an approach remains to be applied to IVDD. Here, the stage\u2010 specific analysis of IVDD in relation to Pfirrmann grading revealed a key transition in immune cells from a preponderance of LCN2\n                    <jats:sup>high<\/jats:sup>\n                    myeloid\u2010derived suppressor cells (MDSCs) during early degeneration to a surge of proinflammatory IL1B+ macrophages in advanced IVDD. scDRS implicated IL1B+ M1\u2010like macrophages as a GWAS risk\u2010enriched subpopulation associated with disease, while functional validation indicated an immunomodulatory effect of LCN2\n                    <jats:sup>high<\/jats:sup>\n                    MDSCs via ANXA1\u2010mediated inflammation suppression. Accordingly, LCN2 knockout mice exhibit accelerated IVDD, whereas recombinant LCN2 promoted macrophage polarization in vitro to the reparative phenotype by enhancing ANXA1 \/ Arginase\u20101 expression and countering LPS\/IFN\u2010\u03b3\u2010induced pro\u2010inflammatory phenotype. This work identifies LCN2\n                    <jats:sup>high<\/jats:sup>\n                    MDSCs as an immunoprotective subpopulation in early IVDD and highlights a potential role of LCN2 as a novel therapeutic agent.\n                  <\/jats:p>","DOI":"10.1002\/advs.202500505","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T15:14:01Z","timestamp":1750950841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identifying Myeloid\u2010Derived Suppressor Cells and Lipocalin\u20102 as Therapeutic Targets for Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0787-8276","authenticated-orcid":false,"given":"Changmeng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics and Traumatology School of Clinical Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong  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Shing","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacy Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3480-371X","authenticated-orcid":false,"given":"Graham Ka Hon","family":"Shea","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology School of Clinical Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong Hong 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