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The dysfunction of immune cells causes HBV to escape immune surveillance and eradication. Increasing evidence has revealed the molecular and cellular mechanisms of the induction of T\u2010cell exhaustion during chronic viral persistence. However, the exact mechanisms of T cell exhaustion during chronic persistence of HBV infection are not fully understood. In this study, we analyzed the expression of inhibitory receptors and the exhausted status of liver T cells in a murine model with persistent HBV. We observed higher expression of the inhibitory receptors PD\u20101, LAG\u20103, and CD160 on liver CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells accompanied by lower production of IFN\u2010\u03b3 and TNF\u2010\u03b1 in HBV persistence mice. T cell\u2010specific deficiency of the transcription factor Eomes significantly decreased the expression of the inhibitory receptors, restored the cytokine production of hepatic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and promoted HBV clearance. Similar phenomena were observed in peripheral blood CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from CHB patients. Mechanistically, Eomes not only directly promoted CD160 expression but also indirectly facilitated the coexpression of inhibitory receptors (PD\u20101, LAG\u20103, CD160) and T cell exhaustion by enhancing the transcription capacity of other key transcription factors (NFATc1, Blimp1, and FoxO1). These findings provide insight into the transcriptional regulation mechanisms of T cell exhaustion during chronic persistence of HBV and suggest novel therapeutic targets to reverse T cell exhaustion and eradicate HBV persistence.\n                  <\/jats:p>","DOI":"10.1111\/febs.16342","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T19:25:19Z","timestamp":1641410719000},"page":"3241-3261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The transcription factor Eomes promotes expression of inhibitory receptors on hepatic CD8\n                    <sup>+<\/sup>\n                    T cells during HBV persistence"],"prefix":"10.1111","volume":"289","author":[{"given":"Linyan","family":"Yu","sequence":"first","affiliation":[{"name":"Institute of Immunopharmaceutical Sciences School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University  Jinan 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