{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:15:55Z","timestamp":1788336955486,"version":"build-2803163510"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Macrophages play an important role in disease progression of pediatric cholestatic liver disease, particularly biliary atresia (BA); however, the restorative versus pathogenic role for precise macrophage subsets remains poorly defined. We aimed to distinguish the transcriptional profiles and roles of defined macrophage subset(s) in murine BA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used multiparameter flow cytometry and RNA-sequencing analysis to profile recruited CD11b\n                      <jats:sup>hi<\/jats:sup>\n                      CD64+ hepatic macrophages by cell surface expression of MHCII and Ly6c in the Rhesus rotavirus (RRV)-induced murine model of BA versus saline controls. Modulation of macrophage numbers via intra-peritoneal injections of clodronate-loaded liposomes was performed to determine the association between macrophage numbers and histologic injury (Ishak score).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ly6c+ macrophages demonstrated the greatest increase in numbers and percent of total macrophages in murine BA versus saline controls whereas MHCII+ macrophages decreased. Transcriptional changes in murine BA MHCII+ macrophages included reduced expression of the Kupffer cell gene signature, lower expression of genes involved in homeostatic processes, and increased expression of genes involved in inflammatory processes. Ly6c+ macrophages in murine BA showed increased expression for\n                      <jats:italic>Hif1a<\/jats:italic>\n                      and other genes involved in the cellular response to hypoxia. Among all subsets, the number of Ly6c+ macrophages exhibited the strongest correlation with severity of histologic liver injury by Ishak score.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data identify specific pathways upregulated in Ly6c vs MHCII+ macrophage subsets in murine BA. Transcriptional similarities between murine BA and human cholestatic macrophages may enable translation of future mechanistic studies to new macrophage subset-specific therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1506195","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T01:25:55Z","timestamp":1738200355000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Transcriptional analysis of murine biliary atresia identifies macrophage heterogeneity and subset-specific macrophage functions"],"prefix":"10.3389","volume":"16","author":[{"given":"Kyle 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