Enhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M.

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dc.contributor.authorRothschild, Daniel E.en
dc.contributor.authorZhang, Yaoen
dc.contributor.authorDiao, Naen
dc.contributor.authorLee, Christina K.en
dc.contributor.authorChen, Keqiangen
dc.contributor.authorCaswell, Clayton C.en
dc.contributor.authorSlade, Daniel J.en
dc.contributor.authorHelm, Richard F.en
dc.contributor.authorLeRoith, Tanyaen
dc.contributor.authorLi, Liwuen
dc.contributor.authorAllen, Irving C.en
dc.contributor.departmentBiochemistryen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2017-01-17T02:56:37Zen
dc.date.available2017-01-17T02:56:37Zen
dc.date.issued2016-12-03en
dc.description.abstractAberrant inflammation is a hallmark of inflammatory bowel disease (IBD) and colorectal cancer. IRAK-M is a critical negative regulator of TLR signaling and overzealous inflammation. Here we utilize data from human studies and Irak-m(-/-) mice to elucidate the role of IRAK-M in the modulation of gastrointestinal immune system homeostasis. In human patients, IRAK-M expression is up-regulated during IBD and colorectal cancer. Further functional studies in mice revealed that Irak-m(-/-) animals are protected against colitis and colitis associated tumorigenesis. Mechanistically, our data revealed that the gastrointestinal immune system of Irak-m(-/-) mice is highly efficient at eliminating microbial translocation following epithelial barrier damage. This attenuation of pathogenesis is associated with expanded areas of gastrointestinal associated lymphoid tissue (GALT), increased neutrophil migration, and enhanced T-cell recruitment. Further evaluation of Irak-m(-/-) mice revealed a splice variant that robustly activates NF-κB signaling. Together, these data identify IRAK-M as a potential target for future therapeutic intervention.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.ebiom.2016.11.039en
dc.identifier.eissn2352-3964en
dc.identifier.urihttp://hdl.handle.net/10919/74352en
dc.language.isoenen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/27939424en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectColitisen
dc.subjectColitis associated canceren
dc.subjectGALTen
dc.subjectIRAK-Men
dc.subjectInflammatory bowel diseaseen
dc.titleEnhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M.en
dc.title.serialEBioMedicineen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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