{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:07:09Z","timestamp":1775797629799,"version":"3.50.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"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>Introduction<\/jats:title>\n                    <jats:p>Non-alcoholic fatty liver disease (NAFLD) is associated with profound alterations in the hepatic immune microenvironment; however, a comprehensive understanding of immune cell dynamics across disease stages remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an integrative reanalysis of publicly available single-cell transcriptomic datasets from the GEO database, encompassing human liver samples spanning the NAFLD continuum. Candidate immune signatures were validated in independent human cohorts and experimentally induced murine NASH models. A diagnostic classifier leveraging pDC associated gene profiles was developed and rigorously evaluated across multiple validation cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Analysis revealed extensive stage-dependent remodeling of hepatic immune composition, with pDCs exhibiting the most pronounced transcriptional and numerical shifts. Specifically, a unique pDC subset coexpressing GZMB and TPM2 was significantly enriched in human NASH samples. This signature was consistently recapitulated in independent human datasets and murine NASH models. The pDC-derived diagnostic model demonstrated robust performance for NASH identification across all validation cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      GZMB\n                      <jats:sup>+<\/jats:sup>\n                      TPM2\n                      <jats:sup>+<\/jats:sup>\n                      pDCs constitute a conserved, NASH-specific immune signature validated across species. The associated diagnostic model provides a robust, clinically applicable tool for non-invasive NASH identification.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1702007","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T04:25:55Z","timestamp":1775795155000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic immune landscape of NAFLD highlights pDCs as predictive biomarkers for disease progression"],"prefix":"10.3389","volume":"17","author":[{"given":"Guozhen","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary, Pancreas and Spleen Surgery, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region (Guangxi Academy of Medical Sciences)","place":["Nanning, China"]},{"name":"Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Guangxi Medical University","place":["Nanning, 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Academy of Medical Sciences)","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary, Pancreas and Spleen Surgery, The People\u2019s Hospital of Guangxi Zhuang Autonomous Region (Guangxi Academy of Medical Sciences)","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyi","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Guangxi Medical University","place":["Nanning, China"]},{"name":"Key Laboratory of Molecular Pathology for Hepatobiliary Diseases of Guangxi, 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