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dc.contributor.authorStoicov, Calin
dc.contributor.authorFan, Xueli
dc.contributor.authorLiu, Jian Hua
dc.contributor.authorBowen, Glennice N.
dc.contributor.authorWhary, Mark
dc.contributor.authorKurt-Jones, Evelyn A.
dc.contributor.authorHoughton, JeanMarie
dc.date2022-08-11T08:08:47.000
dc.date.accessioned2022-08-23T16:08:18Z
dc.date.available2022-08-23T16:08:18Z
dc.date.issued2009-07-01
dc.date.submitted2010-09-10
dc.identifier.issn1550-6606
dc.identifier.pmid19535625
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32417
dc.description.abstractHelicobacter infection is the primary risk factor for gastric cancer, with the cytokine environment within the gastric mucosa the strongest predictor of disease risk. Elevated TNF-alpha, IL-1beta, and low IL-10 are associated with the highest risk. In this study, we used C57BL/6 mice to identify T-bet as a central regulator of the cytokine environment during Helicobacter felis infection. We infected male and female C57BL/6 and C57BL/6-T-bet knockout (KO) litter mates with H. felis and examined the bacterial colonization, immune response, and mucosal damage at varying time points. T-bet KO mice maintained infection for 15 mo at similar levels to wild-type mice. Infection and immune response did not differ between male and female mice. Despite sustained infection, T-bet KO mice respond with a blunted Th1 response associated with preservation of parietal and chief cells and protection from the development of gastric cancer. Unexpectedly, T-bet KO mice develop a gastric environment that would not be expected based on the phenotype of T-bet KO CD4 cells alone. T-bet KO mice respond to H. felis infection with a markedly blunted IL-1beta and TNF-alpha and elevated IL-10 levels. Activity of this one master regulator modulates the expression of the key gastric mucosal cytokines associated with gastric cancer and may be a target for therapy to restore immune balance clinically in patients at risk for gastric cancer.
dc.language.isoen_US
dc.publisherAmerican Association of Immunologists
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=19535625&dopt=Abstract">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.4049/jimmunol.0900511
dc.rightsCitation: J Immunol. 2009 Jul 1;183(1):642-9. Epub 2009 Jun 17.
dc.subjectAdenocarcinoma
dc.subjectAnimals
dc.subjectFemale
dc.subjectGastric Mucosa
dc.subjectGenetic Predisposition to Disease
dc.subjectHelicobacter Infections
dc.subjectHelicobacter felis
dc.subjectInterleukin-1beta
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectStomach Neoplasms
dc.subjectT-Box Domain Proteins
dc.subjectTumor Necrosis Factor-alpha
dc.subjectCancer Biology
dc.subjectGastroenterology
dc.subjectImmunopathology
dc.titleT-bet knockout prevents Helicobacter felis-induced gastric cancer
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume183
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_mdphd/17
dc.identifier.contextkey1550259
html.description.abstract<p>Helicobacter infection is the primary risk factor for gastric cancer, with the cytokine environment within the gastric mucosa the strongest predictor of disease risk. Elevated TNF-alpha, IL-1beta, and low IL-10 are associated with the highest risk. In this study, we used C57BL/6 mice to identify T-bet as a central regulator of the cytokine environment during Helicobacter felis infection. We infected male and female C57BL/6 and C57BL/6-T-bet knockout (KO) litter mates with H. felis and examined the bacterial colonization, immune response, and mucosal damage at varying time points. T-bet KO mice maintained infection for 15 mo at similar levels to wild-type mice. Infection and immune response did not differ between male and female mice. Despite sustained infection, T-bet KO mice respond with a blunted Th1 response associated with preservation of parietal and chief cells and protection from the development of gastric cancer. Unexpectedly, T-bet KO mice develop a gastric environment that would not be expected based on the phenotype of T-bet KO CD4 cells alone. T-bet KO mice respond to H. felis infection with a markedly blunted IL-1beta and TNF-alpha and elevated IL-10 levels. Activity of this one master regulator modulates the expression of the key gastric mucosal cytokines associated with gastric cancer and may be a target for therapy to restore immune balance clinically in patients at risk for gastric cancer.</p>
dc.identifier.submissionpathgsbs_mdphd/17
dc.contributor.departmentDepartment of Cancer Biology
dc.contributor.departmentDepartment of Medicine, Division of Gastroenterology
dc.contributor.departmentGraduate School of Biomedical Sciences, MD/PhD Program
dc.contributor.studentStoicov, Calin


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