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Here, we demonstrated that chronic HBV infection disrupted intrahepatic DCs accumulation and activation by suppressing CC chemokine ligand 5 (CCL5) production from hepatic NK cells. Importantly, chronic HBV infection reduced the number of hepatic conventional NK (cNK) cells, the main source of hepatic CCL5, whereas liver\u2010resident NK (LrNK) cells increased and exhibited lower CCL5 expression and immunosuppressive features. Adoptive transfer of CCL5\u2010competent hepatic cNK cells promoted DCs accumulation and activation, enhanced HBV\u2010specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell responses, and facilitated viral clearance. Mechanistically, chronic HBV infection promoted the activation of adenosine A2a receptor (ADORA2A)\/nuclear factor kappa\u2010B (NF\u2010\u03baB) pathway in hepatic NK cells, thereby antagonizing NF\u2010\u03baB activation, reducing the proportion of cNK cells, suppressing CCL5 production, and ultimately impairing hepatic aggregation and activation of DCs, leading to defective anti\u2010HBV immune responses. This study revealed a novel mechanism involved in chronic HBV infection\u2010induced immune tolerance and indicated that targeting the ADORA2A\/NF\u03baB\/CCL5 axis in cNK cells may represent a potential therapeutic strategy for chronic HBV infection.\n                  <\/jats:p>","DOI":"10.1002\/advs.76696","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:51:58Z","timestamp":1784559118000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic HBV Infection Disrupts CCL5\u2010Secreting cNK Cells and Attenuates Liver Accumulation and Activation of DCs and HBV\u2010Specific T Cells"],"prefix":"10.1002","volume":"13","author":[{"given":"Ailu","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine School of Pharmaceutical Sciences Shandong University  Jinan Shandong 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