{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:13Z","timestamp":1787026573607,"version":"build-2736575974"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"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":["2023YFC2308502"],"award-info":[{"award-number":["2023YFC2308502"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172256, 92169105, M-0060, 82202037"],"award-info":[{"award-number":["82172256, 92169105, M-0060, 82202037"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2025AFD795"],"award-info":[{"award-number":["2025AFD795"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018536","name":"National Mega Project on Major Infectious Disease Prevention","doi-asserted-by":"publisher","award":["2026ZD01912302"],"award-info":[{"award-number":["2026ZD01912302"]}],"id":[{"id":"10.13039\/501100018536","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Liver macrophages are master regulators of disease progression and resolution, whose functions transcend the simplistic M1\/M2 dichotomy. This review synthesizes cutting-edge evidence to establish a dynamic, subset-centric paradigm for understanding macrophage plasticity. In acute liver injury, we delineate how temporally segregated subsets (e.g., early CCR2\n                    <jats:sup>+<\/jats:sup>\n                    vs. late MerTK\n                    <jats:sup>+<\/jats:sup>\n                    macrophages) sequentially orchestrate damage and repair. In chronic settings\u2014including HBV infection, MASLD\/MASH, and fibrosis\/cirrhosis\u2014we reveal a complex coexistence of functionally opposed subsets that concurrently drive pathology (e.g.,\n                    <jats:italic>CD9<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>TREM2<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    macrophages) and promote resolution (e.g., CD300E\n                    <jats:sup>+<\/jats:sup>\n                    macrophages). This refined understanding underpins a critical appraisal of the evolving therapeutic landscape, which is pivoting from broad immunosuppression towards precision strategies. These include pharmacological targeting of specific recruitment or signaling pathways, adoptive transfer of reparative subsets, and innovative engineered cell therapies (e.g., signal-converting CAR-Ms). By framing macrophage functional duality within the \u201cfriend or foe\u201d paradigm, this review provides a conceptual framework for developing subset-specific therapies that harness the beneficial while mitigating the harmful faces of hepatic macrophages. We highlight that the key translational challenge lies in mastering macrophage heterogeneity\u2014requiring resolution of\n                    <jats:italic>in vivo<\/jats:italic>\n                    dynamics, cross-species discrepancies, and achievement of durable, context-specific modulation. The future of \u201cmacrophage medicine\u201d hinges on integrating spatial multi-omics and advanced imaging to enable spatiotemporally precise interventions, ultimately leveraging the cell\u2019s inherent plasticity for therapeutic gain.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1814879","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:21:13Z","timestamp":1776140473000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Macrophage duality in liver diseases: heterogeneity, plasticity, and the quest for precision therapeutics"],"prefix":"10.3389","volume":"17","author":[{"given":"Liwei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuecheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Sutte","sequence":"additional","affiliation":[{"name":"Institute for Virology, University Hospital Essen, University of Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengji","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute for Virology, University Hospital Essen, University of Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), School of Basic Medical Sciences, Huashan Hospital, Shanghai Medical College Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongliang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 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