{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T18:58:49Z","timestamp":1793732329736,"version":"4.6.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["DK122737"],"award-info":[{"award-number":["DK122737"]}],"id":[{"id":"10.13039\/501100000272","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 play a role in the development of liver fibrosis progression via the regulation of inflammatory signaling. However, the precise mechanisms of macrophages contributing to liver fibrosis progression remain unclear. Using a preclinical model of CCl4-treated mice, we determined the composition of immune cells and the alteration of inflammatory gene expression. Our findings revealed a significant increase in liver macrophages, particularly those derived from infiltrating blood monocytes, in fibrotic mice. Moreover, the expression levels of type I IFN signature genes such as\n                    <jats:italic>IFN\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>IFN\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>ISG15<\/jats:italic>\n                    ,\n                    <jats:italic>USP18<\/jats:italic>\n                    ,\n                    <jats:italic>Ifi44<\/jats:italic>\n                    ,\n                    <jats:italic>Ifit1<\/jats:italic>\n                    ,\n                    <jats:italic>Ifit2<\/jats:italic>\n                    ,\n                    <jats:italic>IRF3<\/jats:italic>\n                    , and\n                    <jats:italic>IRF7<\/jats:italic>\n                    were elevated in fibrotic mice. To determine the role of type I IFN signaling in liver fibrosis, we administered an IFNAR-1 antibody to block this pathway for 3 days prior to harvesting the liver. Notably, IFNAR-1 blockade reduced macrophage numbers compared to control mice and alleviated liver fibrosis in mice with increased hepatocyte proliferation and apoptosis. The ratio of P-STAT3\/P-STAT1 in monocyte-derived macrophages was increased in the IFNAR-1 blockade group compared to fibrotic mice, and this was related to the appearance of M2 macrophage differentiation. Additionally, single-cell RNA-seq analysis indicated that IFNAR blockade affected inflammatory pathways involved in hepatocyte regeneration and fibrosis prevention. Taken together, IFNAR-1 blockade alleviates liver fibrosis progression by modulating macrophage inflammatory responses. These results provide insights for developing anti-fibrotic therapies against type I IFN signaling.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1528382","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T01:24:51Z","timestamp":1743989091000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Type I IFN receptor blockade alleviates liver fibrosis through macrophage-derived STAT3 signaling"],"prefix":"10.3389","volume":"16","author":[{"given":"Soo-Jeung","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefina","family":"Garcia Diaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Comlekoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young 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