{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:16:33Z","timestamp":1793812593016,"version":"4.6.1"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":113,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","award":["R83519"],"award-info":[{"award-number":["R83519"]}],"id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["108906\/Z\/15\/Z"],"award-info":[{"award-number":["108906\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["MR\/J010766\/1"],"award-info":[{"award-number":["MR\/J010766\/1"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Inflamm"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute and chronic liver diseases are rising contributors of the worldwide healthcare burden. Inflammation plays a key role in progression of both acute and chronic disease, and effective treatments are limited. Macrophages, a diverse population of professional phagocytes, are required for the timely resolution of tissue injury and are an emerging target to treat acute and chronic liver disease. Colony stimulating factor 1 (CSF1), promotes differentiation and survival of macrophages, which are essential in epithelial regeneration, but the CSF1 protein is rapidly eliminated in vivo. We therefore fused human CSF1 genetically to a modified mouse IgG2a Fc region and transiently expressed this in HEK293-6E cells. The protein was purified from culture supernatant to obtain\u2009&gt;\u200997% monomeric purity, suitable for in vivo testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The nascent hCSF1-Fc fusion proteins were evaluated in vitro and in murine models of health and liver disease. hCSF1-mFc is pharmacologically active in healthy mice, resulting in increases in liver and spleen mass closely reflecting changes in tissue macrophage content. In an acetaminophen-induced acute liver injury model, hCSF1-mFc treatment increased hepatic macrophage accumulation at necrotic sites, reduced serum ALT activity, and serum IL-1\u03b2 levels, and restored white blood cell counts within 72\u00a0h. Furthermore, hCSF1-mFc treatment also increased hepatic macrophage numbers in a carbon tetrachloride (CCl\n                      <jats:sub>4<\/jats:sub>\n                      )-induced liver fibrosis model corresponding with a striking 3.5-fold increased uptake of a soluble phagocytic label, indicating improved hepatic clearance capacity. hCSF1-mFc was also tested in a model of acute on chronic liver injury, which included a bolus delivery of proinflammatory\n                      <jats:italic>E. coli<\/jats:italic>\n                      -coated bioparticles to pre-existing fibrosis. Here, hCSF1-mFc treatment restored body weight, induced hepatomegaly, and reduced several plasma pro-inflammatory cytokines, suggesting reduction of systemic inflammation. Finally, immunofluorescence staining showed hCSF1-mFc treatment induced significant hepatocyte proliferation in healthy and all liver disease models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This report demonstrates that hCSF1-mFc treatment increases liver macrophage populations, improves phagocytic capacity, and stimulates hepatocyte proliferation in experimental liver disease models. hCSF1-based fusion protein therapy might represent a novel immune-based strategy to treat acute and chronic liver disease in the clinic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12950-026-00507-8","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T08:55:04Z","timestamp":1782377704000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Administration of human macrophage colony-stimulating factor-mFc fusion protein increases macrophage phagocytic capacity and stimulates liver regeneration in mice"],"prefix":"10.1186","volume":"23","author":[{"given":"Philip J.","family":"Starkey Lewis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1143-9011","authenticated-orcid":false,"given":"Jennifer A.","family":"Cartwright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Campana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit U.","family":"Baumgarten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilmar","family":"Ebersbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Gabrielle","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Marszalek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Stutchfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhona","family":"Aird","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak-Yung","family":"Man","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eoghan","family":"O\u2019Duibhir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Seuwen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J.","family":"Forbes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"507_CR1","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","volume":"79","author":"H Devarbhavi","year":"2023","unstructured":"Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of liver disease: 2023 update. J Hepatol. 2023;79:516\u201337. https:\/\/doi.org\/10.1016\/j.jhep.2023.03.017.","journal-title":"J Hepatol"},{"key":"507_CR2","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1136\/flgastro-2019-101215","volume":"11","author":"C Millson","year":"2020","unstructured":"Millson C, Considine A, Cramp ME, Holt A, Hubscher S, Hutchinson J, et al. Adult liver transplantation: A UK clinical guideline - part 1: pre-operation. Frontline Gastroenterol. 2020;11:375\u201384. https:\/\/doi.org\/10.1136\/flgastro-2019-101215.","journal-title":"Frontline Gastroenterol"},{"key":"507_CR3","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.4254\/wjh.v9.i36.1315","volume":"9","author":"CE Kling","year":"2017","unstructured":"Kling CE, Perkins JD, Carithers RL, Donovan DM, Sibulesky L. Recent trends in liver transplantation for alcoholic liver disease in the United States. World J Hepatol. 2017;9:1315\u201321. https:\/\/doi.org\/10.4254\/wjh.v9.i36.1315.","journal-title":"World J Hepatol"},{"key":"507_CR4","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.4254\/wjh.v7.i10.1355","volume":"7","author":"M Moini","year":"2015","unstructured":"Moini M, Schilsky ML, Tichy EM. Review on immunosuppression in liver transplantation. World J Hepatol. 2015;7:1355\u201368. https:\/\/doi.org\/10.4254\/wjh.v7.i10.1355.","journal-title":"World J Hepatol"},{"key":"507_CR5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12915-017-0392-4","volume":"15","author":"S Gordon","year":"2017","unstructured":"Gordon S, Pluddemann A. Tissue macrophages: heterogeneity and functions. BMC Biol. 2017;15:53. https:\/\/doi.org\/10.1186\/s12915-017-0392-4.","journal-title":"BMC Biol"},{"key":"507_CR6","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1136\/gut.23.4.265","volume":"23","author":"J Canalese","year":"1982","unstructured":"Canalese J, Gove CD, Gimson AE, Wilkinson SP, Wardle EN, Williams R. Reticuloendothelial system and hepatocytic function in fulminant hepatic failure. Gut. 1982;23:265\u20139.","journal-title":"Gut"},{"key":"507_CR7","doi-asserted-by":"publisher","first-page":"344","DOI":"10.4049\/jimmunol.1400574","volume":"193","author":"E Zigmond","year":"2014","unstructured":"Zigmond E, Samia-Grinberg S, Pasmanik-Chor M, Brazowski E, Shibolet O, Halpern Z, et al. Infiltrating monocyte-derived macrophages and resident kupffer cells display different ontogeny and functions in acute liver injury. J Immunol. 2014;193:344\u201353. https:\/\/doi.org\/10.4049\/jimmunol.1400574.","journal-title":"J Immunol"},{"key":"507_CR8","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1189\/jlb.0308173","volume":"84","author":"MP Holt","year":"2008","unstructured":"Holt MP, Cheng L, Ju C. Identification and characterization of infiltrating macrophages in acetaminophen-induced liver injury. J Leukoc Biol. 2008;84:1410\u201321. https:\/\/doi.org\/10.1189\/jlb.0308173.","journal-title":"J Leukoc Biol"},{"key":"507_CR9","doi-asserted-by":"crossref","unstructured":"Martin Mateos R, Albillos A. Sepsis in patients with cirrhosis awaiting liver transplantation: new trends and management. Liver Transpl. 2019;25.","DOI":"10.1002\/lt.25621"},{"key":"507_CR10","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1053\/jhep.2000.17687","volume":"32","author":"N Rolando","year":"2000","unstructured":"Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology. 2000;32:734\u20139. https:\/\/doi.org\/10.1053\/jhep.2000.17687.","journal-title":"Hepatology"},{"key":"507_CR11","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1136\/gutjnl-2012-302339","volume":"61","author":"JS Bajaj","year":"2012","unstructured":"Bajaj JS, O\u2019Leary JG, Wong F, Reddy KR, Kamath PS. Bacterial infections in end-stage liver disease: current challenges and future directions. Gut. 2012;61:1219\u201325. https:\/\/doi.org\/10.1136\/gutjnl-2012-302339.","journal-title":"Gut"},{"key":"507_CR12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/s1590-8658(01)80134-1","volume":"33","author":"M Borzio","year":"2001","unstructured":"Borzio M, Salerno F, Piantoni L, Cazzaniga M, Angeli P, Bissoli F, et al. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study. Dig Liver Dis. 2001;33:41\u20138. https:\/\/doi.org\/10.1016\/s1590-8658(01)80134-1.","journal-title":"Dig Liver Dis"},{"key":"507_CR13","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1002\/bjs.1800800124","volume":"80","author":"XD Wang","year":"1993","unstructured":"Wang XD, Soltesz V, Andersson R, Bengmark S. Bacterial translocation in acute liver failure induced by 90 per cent hepatectomy in the rat. Br J Surg. 1993;80:66\u201371.","journal-title":"Br J Surg"},{"key":"507_CR14","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1016\/j.jhep.2017.02.026","volume":"66","author":"F Tacke","year":"2017","unstructured":"Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol. 2017;66:1300\u201312. https:\/\/doi.org\/10.1016\/j.jhep.2017.02.026.","journal-title":"J Hepatol"},{"key":"507_CR15","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1002\/hep.24315","volume":"53","author":"JA Thomas","year":"2011","unstructured":"Thomas JA, Pope C, Wojtacha D, Robson AJ, Gordon-Walker TT, Hartland S, et al. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology. 2011;53:2003\u201315. https:\/\/doi.org\/10.1002\/hep.24315.","journal-title":"Hepatology"},{"key":"507_CR16","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.jcyt.2017.05.009","volume":"19","author":"AR Fraser","year":"2017","unstructured":"Fraser AR, Pass C, Burgoyne P, Atkinson A, Bailey L, Laurie A, et al. Development, functional characterization and validation of methodology for GMP-compliant manufacture of phagocytic macrophages: A novel cellular therapeutic for liver cirrhosis. Cytotherapy. 2017;19:1113\u201324. https:\/\/doi.org\/10.1016\/j.jcyt.2017.05.009.","journal-title":"Cytotherapy"},{"key":"507_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jhep.2020.02.031","volume":"73","author":"PS Lewis","year":"2020","unstructured":"Lewis PS, Campana L, Aleksieva N, Cartwright JA, Mackinnon A, O\u2019Duibhir E, et al. Alternatively activated macrophages promote resolution of necrosis following acute liver injury. J Hepatol. 2020;73:1\u201312. https:\/\/doi.org\/10.1016\/j.jhep.2020.02.031.","journal-title":"J Hepatol"},{"key":"507_CR18","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1688502","author":"PJ Starkey Lewis","year":"2019","unstructured":"Starkey Lewis PJ, Moroni F, Forbes SJ. Macrophages as a Cell-Based Therapy for Liver Disease. Semin Liver Dis. 2019. https:\/\/doi.org\/10.1055\/s-0039-1688502.","journal-title":"Semin Liver Dis"},{"key":"507_CR19","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1038\/s41591-019-0599-8","volume":"25","author":"F Moroni","year":"2019","unstructured":"Moroni F, Dwyer BJ, Graham C, Pass C, Bailey L, Ritchie L, et al. Safety profile of autologous macrophage therapy for liver cirrhosis. Nat Med. 2019;25:1560\u20135. https:\/\/doi.org\/10.1038\/s41591-019-0599-8.","journal-title":"Nat Med"},{"key":"507_CR20","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/0092-8674(82)90376-2","volume":"28","author":"RJ Tushinski","year":"1982","unstructured":"Tushinski RJ, Oliver IT, Guilbert LJ, Tynan PW, Warner JR, Stanley ER. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell. 1982;28:71\u201381. https:\/\/doi.org\/10.1016\/0092-8674(82)90376-2.","journal-title":"Cell"},{"key":"507_CR21","doi-asserted-by":"publisher","first-page":"13694","DOI":"10.1074\/jbc.M112.355610","volume":"287","author":"W Yu","year":"2012","unstructured":"Yu W, Chen J, Xiong Y, Pixley FJ, Yeung YG, Stanley ER. Macrophage proliferation is regulated through CSF-1 receptor tyrosines 544, 559, and 807. J Biol Chem. 2012;287:13694\u2013704. https:\/\/doi.org\/10.1074\/jbc.M112.355610.","journal-title":"J Biol Chem"},{"key":"507_CR22","doi-asserted-by":"publisher","first-page":"eadd4374","DOI":"10.1126\/sciimmunol.add4374","volume":"8","author":"JG McKendrick","year":"2024","unstructured":"McKendrick JG, Jones G-R, Elder SS, Watson E, T\u2019Jonck W, Mercer E, et al. CSF1R-dependent macrophages in the salivary gland are essential for epithelial regeneration after radiation-induced injury. Sci Immunol. 2024;8:eadd4374. https:\/\/doi.org\/10.1126\/sciimmunol.add4374.","journal-title":"Sci Immunol"},{"key":"507_CR23","doi-asserted-by":"publisher","first-page":"6179","DOI":"10.1073\/pnas.84.17.6179","volume":"84","author":"A Bartocci","year":"1987","unstructured":"Bartocci A, Mastrogiannis DS, Migliorati G, Stockert RJ, Wolkoff AW, Stanley ER. Macrophages specifically regulate the concentration of their own growth factor in the circulation. Proc Natl Acad Sci U S A. 1987;84:6179\u201383.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"507_CR24","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1038\/mt.2014.112","volume":"22","author":"DJ Gow","year":"2014","unstructured":"Gow DJ, Sauter KA, Pridans C, Moffat L, Sehgal A, Stutchfield BM, et al. Characterisation of a novel Fc conjugate of macrophage colony-stimulating factor. Mol Ther. 2014;22:1580\u201392. https:\/\/doi.org\/10.1038\/mt.2014.112.","journal-title":"Mol Ther"},{"key":"507_CR25","doi-asserted-by":"publisher","first-page":"G533","DOI":"10.1152\/ajpgi.00116.2016","volume":"311","author":"KA Sauter","year":"2016","unstructured":"Sauter KA, Waddell LA, Lisowski ZM, Young R, Lefevre L, Davis GM, et al. Macrophage colony-stimulating factor (CSF1) controls monocyte production and maturation and the steady-state size of the liver in pigs. Am J Physiol Gastrointest Liver Physiol. 2016;311:G533\u201347. https:\/\/doi.org\/10.1152\/ajpgi.00116.2016.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"507_CR26","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1053\/j.gastro.2015.08.053","volume":"149","author":"BM Stutchfield","year":"2015","unstructured":"Keshvari S, Masson JJR, Ferrari-Cestari M, Bodea LG, Nooru-Mohamed F, Tse BWC, et al. Am J Physiol Endocrinol Metab. 2024;326(2):E149\u2013165. https:\/\/doi.org\/10.1053\/j.gastro.2015.08.053.\u00a0Epub 2023 Dec 20.\u00a0PMID: 38117267.","journal-title":"Gastroenterology"},{"key":"507_CR27","doi-asserted-by":"publisher","first-page":"dmm049387","DOI":"10.1242\/dmm.049387","volume":"15","author":"S Keshvari","year":"2022","unstructured":"Keshvari S, Genz B, Teakle N, Caruso M, Cestari MF, Patkar OL, et al. Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease. Dis Model Mech. 2022;15:dmm049387. https:\/\/doi.org\/10.1242\/dmm.049387.","journal-title":"Dis Model Mech"},{"key":"507_CR28","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.molimm.2014.09.017","volume":"63","author":"E Arduin","year":"2015","unstructured":"Arduin E, Arora S, Bamert PR, Kuiper T, Popp S, Geisse S, et al. Highly reduced binding to high and low affinity mouse Fc gamma receptors by L234A\/L235A and N297A Fc mutations engineered into mouse IgG2a. Mol Immunol. 2015;63:456\u201363. https:\/\/doi.org\/10.1016\/j.molimm.2014.09.017.","journal-title":"Mol Immunol"},{"key":"507_CR29","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.4049\/jimmunol.1701247","volume":"200","author":"L Campana","year":"2018","unstructured":"Campana L, Starkey Lewis PJ, Pellicoro A, Aucott RL, Man J, O\u2019Duibhir E, et al. The STAT3-IL-10-IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury. J Immunol. 2018;200:1169\u201387. https:\/\/doi.org\/10.4049\/jimmunol.1701247.","journal-title":"J Immunol"},{"key":"507_CR30","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1093\/clinchem\/20.4.447","volume":"20","author":"FC Pearlman","year":"1974","unstructured":"Pearlman FC, Lee RT. Detection and measurement of total bilirubin in serum, with use of surfactants as solubilizing agents. Clin Chem. 1974;20:447\u201353.","journal-title":"Clin Chem"},{"key":"507_CR31","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1093\/clinchem\/24.1.58","volume":"24","author":"HU Bergmeyer","year":"1978","unstructured":"Bergmeyer HU, Scheibe P, Wahlefeld AW. Optimization of methods for aspartate aminotransferase and alanine aminotransferase. Clin Chem. 1978;24:58\u201373.","journal-title":"Clin Chem"},{"key":"507_CR32","doi-asserted-by":"publisher","first-page":"362","DOI":"10.30802\/AALAS-JAALAS-18-000064","volume":"58","author":"DB S\u00f8rensen","year":"2019","unstructured":"S\u00f8rensen DB, Metzdorff SB, Jensen LK, Andersen KH, Teilmann AC, Jensen HE, et al. Time-dependent pathologic and inflammatory consequences of various blood sampling techniques in mice. J Am Assoc Lab Anim Sci. 2019;58:362\u201372. https:\/\/doi.org\/10.30802\/AALAS-JAALAS-18-000064.","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"507_CR33","doi-asserted-by":"publisher","unstructured":"Beljaars L, Schippers M, Reker-Smit C, Martinez FO, Helming L, Poelstra K, et al. Hepatic localization of macrophage phenotypes during fibrogenesis and resolution of fibrosis in mice and humans. Front Immunol. 2014;5. https:\/\/doi.org\/10.3389\/fimmu.2014.00430.","DOI":"10.3389\/fimmu.2014.00430"},{"key":"507_CR34","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41577-024-01098-2","volume":"25","author":"S Can\u00e8","year":"2025","unstructured":"Can\u00e8 S, Geiger R, Bronte V. The roles of arginases and arginine in immunity. Nat Rev Immunol. 2025;25:266\u201384. https:\/\/doi.org\/10.1038\/s41577-024-01098-2.","journal-title":"Nat Rev Immunol"},{"key":"507_CR35","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nrc2657","volume":"9","author":"T Abbas","year":"2009","unstructured":"Abbas T, Dutta A. P21 in cancer: Intricate networks and multiple activities. Nat Rev Cancer. 2009;9:400\u201314. https:\/\/doi.org\/10.1038\/nrc2657.","journal-title":"Nat Rev Cancer"},{"key":"507_CR36","doi-asserted-by":"publisher","unstructured":"Jalan R, Fernandez J, Wiest R, Schnabl B, Moreau R, Angeli P, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol. 2014;60:1310\u201324. https:\/\/doi.org\/10.1016\/j.jhep.2014.01.024.","DOI":"10.1016\/j.jhep.2014.01.024"},{"key":"507_CR37","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1136\/gutjnl-2017-314240","volume":"67","author":"J Fernandez","year":"2018","unstructured":"Fernandez J, Acevedo J, Wiest R, Gustot T, Amoros A, Deulofeu C, et al. Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut. 2018;67:1870\u201380. https:\/\/doi.org\/10.1136\/gutjnl-2017-314240.","journal-title":"Gut"},{"key":"507_CR38","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1097\/HEP.0000000000000458","volume":"78","author":"RT Stravitz","year":"2023","unstructured":"Stravitz RT, Fontana RJ, Karvellas C, Durkalski V, McGuire B, Rule JA, et al. Acute Liver Failure Study Group. Future directions in acute liver failure. Hepatology. 2023;78:1266\u201389. https:\/\/doi.org\/10.1097\/HEP.0000000000000458.","journal-title":"Hepatology"},{"key":"507_CR39","doi-asserted-by":"publisher","first-page":"G388","DOI":"10.1152\/ajpgi.00343.2017","volume":"314","author":"C Pridans","year":"2018","unstructured":"Pridans C, Sauter KA, Irvine KM, Davis GM, Lefevre L, Raper A, et al. Macrophage colony-stimulating factor increases hepatic macrophage content, liver growth, and lipid accumulation in neonatal rats. Am J Physiol Gastrointest Liver Physiol. 2018;314:G388\u201398. https:\/\/doi.org\/10.1152\/ajpgi.00343.2017.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"507_CR40","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.cyto.2012.08.008","volume":"60","author":"DJ Gow","year":"2012","unstructured":"Gow DJ, Garceau V, Kapetanovic R, Sester DP, Fici GJ, Shelly JA, et al. Cloning and expression of porcine Colony Stimulating Factor-1 (CSF-1) and Colony Stimulating Factor-1 Receptor (CSF-1R) and analysis of the species specificity of stimulation by CSF-1 and Interleukin 34. Cytokine. 2012;60:793\u2013805. https:\/\/doi.org\/10.1016\/j.cyto.2012.08.008.","journal-title":"Cytokine"},{"key":"507_CR41","first-page":"155","volume":"49","author":"ES Kawasaki","year":"1990","unstructured":"Kawasaki ES, Ladner MB. Molecular biology of macrophage colony-stimulating factor. Immunol Ser. 1990;49:155\u201376.","journal-title":"Immunol Ser"},{"key":"507_CR42","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1084\/jem.20120412","volume":"210","author":"J Luo","year":"2013","unstructured":"Luo J, Elwood F, Britschgi M, Villeda S, Zhang H, Ding Z, et al. Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival. J Exp Med. 2013;210:157\u201372. https:\/\/doi.org\/10.1084\/jem.20120412.","journal-title":"J Exp Med"},{"key":"507_CR43","doi-asserted-by":"publisher","first-page":"4930","DOI":"10.1182\/blood-2005-10-4144","volume":"107","author":"W Xu","year":"2006","unstructured":"Xu W, Roos A, Schlagwein N, Woltman AM, Daha MR, van Kooten C. IL-10\u2013producing macrophages preferentially clear early apoptotic cells. Blood. 2006;107:4930\u20137. https:\/\/doi.org\/10.1182\/blood-2005-10-4144.","journal-title":"Blood"},{"key":"507_CR44","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1172\/JCI35958","volume":"119","author":"AB Imaeda","year":"2009","unstructured":"Imaeda AB, Watanabe A, Sohail MA, Mahmood S, Mohamadnejad M, Sutterwala FS, et al. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J Clin Invest. 2009;119:305\u201314. https:\/\/doi.org\/10.1172\/JCI35958.","journal-title":"J Clin Invest"},{"key":"507_CR45","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.ajpath.2011.03.029","volume":"179","author":"ZA Radi","year":"2011","unstructured":"Radi ZA, Koza-Taylor PH, Bell RR, Obert LA, Runnels HA, Beebe JS, et al. Increased serum enzyme levels associated with kupffer cell reduction with no signs of hepatic or skeletal muscle injury. Am J Pathol. 2011;179:240\u20137. https:\/\/doi.org\/10.1016\/j.ajpath.2011.03.029.","journal-title":"Am J Pathol"},{"key":"507_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0074-7696(01)12002-4","volume":"212","author":"N Platt","year":"2002","unstructured":"Platt N, Haworth R, Darley L, Gordon S. The many roles of the class A macrophage scavenger receptor. Int Rev Cytol. 2002;212:1\u201340. https:\/\/doi.org\/10.1016\/s0074-7696(01)12002-4.","journal-title":"Int Rev Cytol"},{"key":"507_CR47","doi-asserted-by":"publisher","first-page":"G579","DOI":"10.1152\/ajpgi.1992.263.4.G579","volume":"263","author":"P Akerman","year":"1992","unstructured":"Akerman P, Cote P, Yang SQ, McClain C, Nelson S, Bagby GJ, et al. Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. Am J Physiol. 1992;263:G579\u201385. https:\/\/doi.org\/10.1152\/ajpgi.1992.263.4.G579.","journal-title":"Am J Physiol"},{"key":"507_CR48","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41575-020-0342-4","volume":"18","author":"GK Michalopoulos","year":"2021","unstructured":"Michalopoulos GK, Bhushan B. Liver regeneration: biological and pathological mechanisms and implications. Nat Rev Gastroenterol Hepatol. 2021;18:40\u201355. https:\/\/doi.org\/10.1038\/s41575-020-0342-4.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"507_CR49","doi-asserted-by":"publisher","first-page":"110255","DOI":"10.1016\/j.cbi.2022.110255","volume":"369","author":"BP Awasthi","year":"2023","unstructured":"Awasthi BP, Guragain D, Chaudhary P, Jee J-G, Kim J-A, Jeong B-S. Antitumor activity of a pexidartinib bioisostere inhibiting CSF1 production and CSF1R kinase activity in human hepatocellular carcinoma. Chem Biol Interact. 2023;369:110255. https:\/\/doi.org\/10.1016\/j.cbi.2022.110255.","journal-title":"Chem Biol Interact"},{"key":"507_CR50","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.21037\/atm-21-539","volume":"9","author":"A Eresen","year":"2021","unstructured":"Eresen A, Yang J, Scotti A, Cai K, Yaghmai V, Zhang Z. Combination of natural killer cell-based immunotherapy and irreversible electroporation for the treatment of hepatocellular carcinoma. Ann Transl Med. 2021;9:1089\u20131089. https:\/\/doi.org\/10.21037\/atm-21-539.","journal-title":"Ann Transl Med"},{"key":"507_CR51","doi-asserted-by":"publisher","unstructured":"Odagiri N, Matsubara T, Sato-Matsubara M, Fujii H, Enomoto M, Kawada N. Anti-fibrotic treatments for chronic liver diseases: The present and the future. Clin Mol Hepatol. 2021;27. https:\/\/doi.org\/10.3350\/cmh.2020.0187.","DOI":"10.3350\/cmh.2020.0187"}],"container-title":["Journal of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12950-026-00507-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12950-026-00507-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12950-026-00507-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:09:05Z","timestamp":1792123745000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12950-026-00507-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["507"],"URL":"https:\/\/doi.org\/10.1186\/s12950-026-00507-8","relation":{},"ISSN":["1476-9255"],"issn-type":[{"value":"1476-9255","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]},"assertion":[{"value":"30 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments were carried out under procedural guide lines, severity protocols and with ethical permission from the University of Edinburgh Animal Welfare and Ethical Review Body and the Home Office (UK), licence numbers 70\/7847 and P231C5F81.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"There was no competing interests at the time of experiments, however L.C., P.S.L., and S.J.F are shareholders of Resolution Therapeutics Ltd. a macrophage cell therapy developer. S.J.F is a scientific adviser and L.C. is an employee of Resolution Therapeutics.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"27"}}