{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:53:48Z","timestamp":1789480428716,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chemomab Therapeutics Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Primary sclerosing cholangitis (PSC) is an inflammatory and fibrotic biliary disease lacking approved treatment. We studied CCL24, a chemokine shown to be overexpressed in damaged bile ducts, and its involvement in key disease-related mechanisms. Serum proteomics of PSC patients and healthy controls (HC) were analyzed using the Olink\u00ae proximity extension assay and compared based on disease presence, fibrosis severity, and CCL24 levels. Disease-related canonical pathways, upstream regulators, and toxicity functions were elevated in PSC patients compared to HC and further elevated in patients with high CCL24 levels. In vitro, a protein signature in CCL24-treated hepatic stellate cells (HSCs) differentiated patients by disease severity. In mice, CCL24 intraperitoneal injection selectively recruited neutrophils and monocytes. Treatment with CM-101, a CCL24-neutralizing antibody, in an \u03b1-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model effectively inhibited accumulation of peribiliary neutrophils and macrophages while reducing biliary hyperplasia and fibrosis. Furthermore, in PSC patients, CCL24 levels were correlated with upregulation of monocyte and neutrophil chemotaxis pathways. Collectively, these findings highlight the distinct role of CCL24 in PSC, influencing disease-related mechanisms, affecting immune cells trafficking and HSC activation. Its blockade with CM-101 reduces inflammation and fibrosis and positions CCL24 as a promising therapeutic target in PSC.<\/jats:p>","DOI":"10.3390\/cells13030209","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T07:22:32Z","timestamp":1705994552000},"page":"209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Role of CCL24 in Primary Sclerosing Cholangitis: Bridging Patient Serum Proteomics to Preclinical Data"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9634-4638","authenticated-orcid":false,"given":"Raanan","family":"Greenman","sequence":"first","affiliation":[{"name":"Chemomab Therapeutics Ltd., Tel Aviv 6158002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Snir","sequence":"additional","affiliation":[{"name":"Chemomab Therapeutics Ltd., Tel Aviv 6158002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi","family":"Katav","sequence":"additional","affiliation":[{"name":"Chemomab Therapeutics Ltd., Tel Aviv 6158002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revital","family":"Aricha","sequence":"additional","affiliation":[{"name":"Chemomab Therapeutics Ltd., Tel Aviv 6158002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbal","family":"Mishalian","sequence":"additional","affiliation":[{"name":"Goldyne Savad Institute of Gene Therapy, Hebrew University Hospital Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ophir","family":"Hay","sequence":"additional","affiliation":[{"name":"Goldyne Savad Institute of Gene Therapy, Hebrew University Hospital Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4321-9055","authenticated-orcid":false,"given":"Matthew","family":"Frankel","sequence":"additional","affiliation":[{"name":"Chemomab Therapeutics Ltd., Tel Aviv 6158002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lawler","sequence":"additional","affiliation":[{"name":"Chemomab Therapeutics Ltd., Tel Aviv 6158002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7635-9931","authenticated-orcid":false,"given":"Francesca","family":"Saffioti","sequence":"additional","affiliation":[{"name":"UCL Institute for Liver and Digestive Health, University College of London, London NW3 2PF, UK"},{"name":"Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London NW3 2QG, UK"},{"name":"Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Pinzani","sequence":"additional","affiliation":[{"name":"UCL Institute for Liver and Digestive Health, University College of London, London NW3 2PF, UK"},{"name":"Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London NW3 2QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Thorburn","sequence":"additional","affiliation":[{"name":"UCL Institute for Liver and Digestive Health, University College of London, London NW3 2PF, UK"},{"name":"Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London NW3 2QG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amnon","family":"Peled","sequence":"additional","affiliation":[{"name":"Goldyne Savad Institute of Gene Therapy, Hebrew University Hospital Jerusalem, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Mor","sequence":"additional","affiliation":[{"name":"Chemomab Therapeutics Ltd., Tel Aviv 6158002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilan","family":"Vaknin","sequence":"additional","affiliation":[{"name":"Chemomab Therapeutics Ltd., Tel Aviv 6158002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.bpg.2011.10.009","article-title":"Pathogenesis of Primary Sclerosing Cholangitis","volume":"25","author":"Pollheimer","year":"2011","journal-title":"Best Pract. 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