{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:04:27Z","timestamp":1789967067651,"version":"4.0.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"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>Background<\/jats:title>\n                    <jats:p>Ischemia-reperfusion injury (IRI) and acute rejection (AR) limit liver transplantation success. Early growth response 1 (EGR1) mediates stress and inflammation, yet its cellular distribution and potential involvement in adaptive alloimmunity during distinct post-transplant stages remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A rat orthotopic liver transplantation model was used to evaluate graft injury and EGR1 spatiotemporal expression during IRI (6\u201324 h) and AR (5\u201310 d). Public scRNA-seq data and virtual knockout analysis were used to assess the cellular distribution and potential regulatory role of\n                      <jats:italic>Egr1<\/jats:italic>\n                      . EGR1-overexpressing bone marrow-derived dendritic cells (BMDCs) were co-cultured with CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cells to assess cytokine secretion, proliferation, and shifted Th17\/Treg differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both syngeneic and allogeneic grafts exhibited early IRI. By days 5\u201310, allografts developed AR with elevated liver enzymes and Banff scores. EGR1 rose transiently during IRI but re-escalated exclusively in allografts during AR, localizing to portal infiltrates. scRNA-seq showed preferential\n                      <jats:italic>Egr1<\/jats:italic>\n                      expression in graft myeloid cells, while virtual knockout suggested immune-related regulatory effects. EGR1-associated APC activation and Th17-associated responses were observed in rejecting allografts. EGR1 overexpression in BMDCs promoted pro-inflammatory cytokine secretion, T-cell proliferation, and altered Th17\/Treg-associated responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EGR1 contributes to liver allograft rejection by modulating myeloid APC responses and Th17\/Treg-associated T-cell responses, highlighting its potential as a therapeutic target for AR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1901189","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:29:16Z","timestamp":1789964956000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Myeloid EGR1 contributes to Th17\/Treg imbalance during acute liver allograft rejection in a rat model"],"prefix":"10.3389","volume":"17","author":[{"given":"Yaming","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Pathology and Institute of Oncology, The School of Basic Medical Sciences, Fujian Medical University","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Institute of Oncology, The School of Basic Medical Sciences, Fujian Medical University","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Institute of Oncology, The School of Basic Medical Sciences, Fujian Medical University","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Institute of Oncology, The School of Basic Medical Sciences, Fujian Medical University","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Institute of Oncology, The School of Basic Medical Sciences, Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Diagnostic Pathology Center, Fujian Medical University","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2200923","article-title":"Liver transplantation","volume":"389","author":"Lucey","year":"2023","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2025.01.022","article-title":"OPTN\/SRTR 2023 annual data report: 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