{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:55:04Z","timestamp":1781812504251,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360108"],"award-info":[{"award-number":["82360108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The immune checkpoint Tim\u20103 has been implicated in the pathogenesis of primary biliary cholangitis (PBC), but its precise role in modulating macrophage polarization and immune dysregulation remains unclear. This study aimed to define the expression patterns of Tim\u20103 in PBC patients and elucidate its functional impact on macrophage behavior and disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bulk RNA sequencing was performed using peripheral blood mononuclear cells (PBMCs) derived from PBC patients. The expression of Tim\u20103 and Toll\u2010like receptor (TLR) 2 was assessed using flow cytometry. A murine model of autoimmune cholangitis was established using syngeneic bile duct protein. The Tim\u20103\/Galectin\u20109 pathway was blocked using \u03b1\u2010lactose both in\u00a0vivo and in\u00a0vitro. Short hairpin RNA (shRNA)\u2013mediated silencing of ATF3 expression was conducted in THP\u20101 cells to explore its role in macrophage regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results revealed a significant pro\u2010inflammatory innate immune response in the periphery of PBC patients. Advanced PBC patients exhibited reduced M2\u2010like Kupffer cells and decreased expression of Tim\u20103 and ATF3, whereas Galectin\u20109 expression was upregulated. TLR2 activation downregulated Tim\u20103 and ATF3 expression in macrophages. Blockade of the Tim\u20103\/Galectin\u20109 pathway with \u03b1\u2010lactose exacerbated experimental autoimmune cholangitis, reduced M2 Kupffer cells and ATF3 expression, and increased CXCL10 levels in the liver. Furthermore, silencing ATF3 impaired the suppressive effects of the Tim\u20103\/Galectin\u20109 pathway on TLR2\u2010activated macrophages and primary murine Kupffer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight the prominent pro\u2010inflammatory innate immune response in PBC patients and demonstrate that ATF3 partially mediates the immunomodulatory effects of the Tim\u20103\/Galectin\u20109 pathway on macrophages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.70234","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:29:48Z","timestamp":1768523388000},"page":"787-802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ATF3 Mediates the Immunoregulatory Role of the Tim\u20103 Pathway in Primary Biliary Cholangitis"],"prefix":"10.1111","volume":"41","author":[{"given":"Jiamin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"},{"name":"Yunnan Liver Disease Research Center  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"},{"name":"Yunnan Liver Disease Research Center  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"},{"name":"Yunnan Liver Disease Research Center  Kunming Yunnan 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