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Dendritic cell- derived TGF- β mediates the induction of mucosal regulatory T- cell response to Helicobacter infection essential for maintenance of immune tolerance in mice

dc.contributor.authorOwyang, Stephanie Y.
dc.contributor.authorZhang, Min
dc.contributor.authorEl‐zaatari, Mohamad
dc.contributor.authorEaton, Kathryn A.
dc.contributor.authorBishu, Shrinivas
dc.contributor.authorHou, Guoqing
dc.contributor.authorGrasberger, Helmut
dc.contributor.authorKao, John Y.
dc.date.accessioned2020-12-02T14:41:53Z
dc.date.availableWITHHELD_13_MONTHS
dc.date.available2020-12-02T14:41:53Z
dc.date.issued2020-12
dc.identifier.citationOwyang, Stephanie Y.; Zhang, Min; El‐zaatari, Mohamad ; Eaton, Kathryn A.; Bishu, Shrinivas; Hou, Guoqing; Grasberger, Helmut; Kao, John Y. (2020). "Dendritic cell- derived TGF- β mediates the induction of mucosal regulatory T- cell response to Helicobacter infection essential for maintenance of immune tolerance in mice." Helicobacter 25(6): n/a-n/a.
dc.identifier.issn1083-4389
dc.identifier.issn1523-5378
dc.identifier.urihttps://hdl.handle.net/2027.42/163641
dc.description.abstractBackgroundHelicobacter pylori infection leads to regulatory T- cell (Treg) induction in infected mice, which contributes to H. pylori immune escape. However, the mechanisms responsible for H. pylori induction of Treg and immune tolerance remain unclear. We hypothesized DC- produced TGF- β may be responsible for Treg induction and immune tolerance.Materials and MethodsTo test this hypothesis, we generated TGF- β- DC mice (CD11c+ DC- specific TGF- β deletion) and assessed the impact of DC- specific TGF- β deletion on DC function during Helicobacter infection in vitro and in vivo. To examine the T cell- independent DC function, we crossed TGF- β- DC mice onto Rag1KO background to generate TGF- β- DCxRag1KO mice.ResultsWhen stimulated with H. pylori, TGF- β- DC BMDC/splenocyte cocultures showed increased levels of proinflammatory cytokines and decreased levels of anti- inflammatory cytokines compared to control, indicating a proinflammatory DC phenotype. Following 6 months of H. felis infection, TGF- β- DC mice developed more severe gastritis and a trend toward more metaplasia compared to TGF- βfl/fl with increased levels of inflammatory Th1 cytokine mRNA and lower gastric H. felis colonization compared to infected TGF- βfl/fl mice. In a T cell- deficient background using TGF- β- DCxRag1KO mice, H. felis colonization was significantly lower when DC- derived TGF- β was absent, revealing a direct, innate function of DC in controlling H. felis infection independent of Treg induction.ConclusionsOur findings indicate that DC- derived TGF- β mediates Helicobacter- induced Treg response and attenuates the inflammatory Th1 response. We also demonstrated a previously unrecognized innate role of DC controlling Helicobacter colonization via a Treg- independent mechanism. DC TGF- β signaling may represent an important target in the management of H. pylori.
dc.publisherWiley Periodicals, Inc.
dc.subject.otherimmune response
dc.subject.otherhelicobacter felis
dc.subject.othergastroenterology
dc.titleDendritic cell- derived TGF- β mediates the induction of mucosal regulatory T- cell response to Helicobacter infection essential for maintenance of immune tolerance in mice
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelInternal Medicine and Specialties
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/163641/2/hel12763.pdfen_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/163641/1/hel12763_am.pdfen_US
dc.identifier.doi10.1111/hel.12763
dc.identifier.sourceHelicobacter
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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