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Here, we investigate the role of <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2 in the tolerogenic programing of dendritic cells in a mouse model of <jats:italic>H. pylori<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2 deficient (<jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) mice and wild\u2010type (Wt) mice infected with <jats:italic>H. pylori <\/jats:italic><jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>1 strain were analyzed by <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">FACS<\/jats:styled-content> analysis. In vitro, bone marrow\u2010derived <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content> on day 6 from <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> and Wt mice cocultured with or without <jats:italic>H. pylori<\/jats:italic> were examined to determine the impact of <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2 signaling on dendritic cells function by <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> ELISA<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">FACS<\/jats:styled-content> analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Acute <jats:italic>H. pylori<\/jats:italic> infection was associated with a threefold increase in <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression in the gastric mucosa. <jats:italic>H. pylori<\/jats:italic>\u2010infected <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and pro\u2010inflammatory cytokine <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels, but lower degree of <jats:italic>H. pylori<\/jats:italic> gastric colonization compared to infected Wt mice. Peripheral <jats:italic>H. pylori<\/jats:italic>\u2010specific immune response measured in the <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> bone marrow\u2010derived DC was less mature and shown a lower Treg\/Th17 ratio. Moreover, blockade of <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2 signaling by <jats:styled-content style=\"fixed-case\">MCP<\/jats:styled-content>\u20101 neutralizing antibody inhibited <jats:italic>H. pylori<\/jats:italic>\u2010stimulated bone marrow\u2010derived DC maturation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2 plays an essential role in <jats:italic>H. pylori<\/jats:italic>\u2010induced immune tolerance and shed light on a novel mechanism of <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>2\u2010dependent <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content> Treg induction, which appears to be important in maintaining mucosal homeostasis during <jats:italic>H. pylori<\/jats:italic> infection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.12366","type":"journal-article","created":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T02:56:52Z","timestamp":1481252212000},"source":"Crossref","is-referenced-by-count":7,"title":["<scp>CCR<\/scp>2 mediates <i>Helicobacter pylori<\/i>\u2010induced immune tolerance and contributes to mucosal homeostasis"],"prefix":"10.1111","volume":"22","author":[{"given":"Xia","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Medicine Shandong University  Jinan Shandong China"},{"name":"Department of Internal Medicine Division of Gastroenterology University of Michigan Health System  Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Gastroenterology University of Michigan Health System  Ann Arbor MI 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