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By comparing the gene expression profile of intrahepatically primed, dysfunctional HBV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells with that of systemically primed, functional effector counterparts, we found that the expression of interferon-stimulated genes (ISGs) is selectively suppressed in the dysfunctional CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. The ISG suppression was associated with impaired phosphorylation of STAT1 in response to IFN-\u03b1 treatment. Importantly, a strong induction of type I interferons (IFN-Is) in the liver facilitated the functional differentiation of intrahepatically primed HBV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in association with the restoration of ISGs\u2019 expression in the T cells. These results suggest that intrahepatic priming suppresses IFN-I signaling in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, which may contribute to the dysfunction. The data also suggest a therapeutic value of the robust induction of intrahepatic IFN-Is for the treatment of chronic HBV infection.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.145761","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T13:10:52Z","timestamp":1609852252000},"source":"Crossref","is-referenced-by-count":13,"title":["Restoration of type I interferon signaling in intrahepatically primed CD8+ T cells promotes functional differentiation"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0985-1111","authenticated-orcid":true,"given":"Keigo","family":"Kawashima","sequence":"first","affiliation":[{"name":"Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan."},{"name":"Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, 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