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The mechanisms underlying natural killer (NK) cell group 2D receptor (NKG2D) that activates NK cells and participates in anti-HBV immunity and immunopathology has not been thoroughly elucidated. Peripheral NKG2D<jats:sup>+<\/jats:sup> and IFN-\u03b3<jats:sup>+<\/jats:sup> NK cells frequencies and intrahepatic NKG2D and IFN-\u03b3 mRNA and protein expressions were determined in HBV-infected patients. Levels of NKG2D and IFN-\u03b3 mRNA and protein in NK cells, co-cultured with HBV-replicating HepG2 cells with or without NKG2D blockade, were analyzed. Serum and supernatant IFN-\u03b3, TNF-\u03b1, perforin and granzyme B were measured. In results, peripheral NKG2D<jats:sup>+<\/jats:sup> and IFN-\u03b3<jats:sup>+<\/jats:sup> NK cells frequencies, intrahepatic NKG2D and IFN-\u03b3 mRNA and protein levels, and serum IFN-\u03b3, TNF-\u03b1, perforin and granzyme B levels were all highest in HBV-related acute-on-chronic liver failure group, followed by chronic hepatitis B and chronic HBV carrier groups. <jats:italic>In vitro<\/jats:italic>, NKG2D and IFN-\u03b3 mRNA and protein levels were higher in NK cells with IFN-\u03b1 stimulation than without stimulation. Supernatant IFN-\u03b3, TNF-\u03b1, perforin and granzyme B levels were increased under co-culture or IFN-\u03b1 stimulating conditions, but were partially blocked by NKG2DmAb. In conclusion, NKG2D regulates immune inflammation and anti-viral response partly through activation of NK cells during HBV infection.<\/jats:p>","DOI":"10.1038\/s41598-017-00221-9","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T12:22:52Z","timestamp":1488370972000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["NKG2D modulates aggravation of liver inflammation by activating NK cells in HBV infection"],"prefix":"10.1038","volume":"7","author":[{"given":"Yadong","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjing","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhu","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianfei","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caiyan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,3,7]]},"reference":[{"key":"221_CR1","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.patbio.2009.11.001","volume":"58","author":"FV Chisari","year":"2010","unstructured":"Chisari, F. 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