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However, the mechanisms responsible for\n                      <jats:italic>H. pylori<\/jats:italic>\n                      induction of Treg and immune tolerance remain unclear. We hypothesized DC\u2010produced TGF\u2010\u03b2 may be responsible for Treg induction and immune tolerance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      To test this hypothesis, we generated TGF\u2010\u03b2\n                      <jats:sup>\u2206DC<\/jats:sup>\n                      mice (CD11c\n                      <jats:sup>+<\/jats:sup>\n                      DC\u2010specific TGF\u2010\u03b2 deletion) and assessed the impact of DC\u2010specific TGF\u2010\u03b2 deletion on DC function during\n                      <jats:italic>Helicobacter<\/jats:italic>\n                      infection in vitro and in vivo. To examine the T cell\u2013independent DC function, we crossed TGF\u2010\u03b2\n                      <jats:sup>\u2206DC<\/jats:sup>\n                      mice onto Rag1KO background to generate TGF\u2010\u03b2\n                      <jats:sup>\u2206DC<\/jats:sup>\n                      xRag1KO mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      When stimulated with\n                      <jats:italic>H. pylori<\/jats:italic>\n                      , TGF\u2010\u03b2\n                      <jats:sup>\u2206DC<\/jats:sup>\n                      BMDC\/splenocyte cocultures showed increased levels of proinflammatory cytokines and decreased levels of anti\u2010inflammatory cytokines compared to control, indicating a proinflammatory DC phenotype. Following 6\u00a0months of\n                      <jats:italic>H. felis<\/jats:italic>\n                      infection, TGF\u2010\u03b2\n                      <jats:sup>\u2206DC<\/jats:sup>\n                      mice developed more severe gastritis and a trend toward more metaplasia compared to TGF\u2010\u03b2\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      with increased levels of inflammatory Th1 cytokine mRNA and lower gastric\n                      <jats:italic>H. felis<\/jats:italic>\n                      colonization compared to infected TGF\u2010\u03b2\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      mice. In a T cell\u2013deficient background using TGF\u2010\u03b2\n                      <jats:sup>\u2206DC<\/jats:sup>\n                      xRag1KO mice,\n                      <jats:italic>H. felis<\/jats:italic>\n                      colonization was significantly lower when DC\u2010derived TGF\u2010\u03b2 was absent, revealing a direct, innate function of DC in controlling\n                      <jats:italic>H. felis<\/jats:italic>\n                      infection independent of Treg induction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings indicate that DC\u2010derived TGF\u2010\u03b2 mediates\n                      <jats:italic>Helicobacter<\/jats:italic>\n                      \u2010induced Treg response and attenuates the inflammatory Th1 response. We also demonstrated a previously unrecognized innate role of DC controlling\n                      <jats:italic>Helicobacter<\/jats:italic>\n                      colonization via a Treg\u2010independent mechanism. DC TGF\u2010\u03b2 signaling may represent an important target in the management of\n                      <jats:italic>H. pylori<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hel.12763","type":"journal-article","created":{"date-parts":[[2020,10,7]],"date-time":"2020-10-07T00:52:46Z","timestamp":1602031966000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Dendritic cell\u2010derived TGF\u2010\u03b2 mediates the induction of mucosal regulatory T\u2010cell response to\n                    <i>Helicobacter<\/i>\n                    infection essential for maintenance of immune tolerance in mice"],"prefix":"10.1111","volume":"25","author":[{"given":"Stephanie Y.","family":"Owyang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine (Division of Gastroenterology) University of Michigan Health System Ann Arbor MI 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