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dc.contributor.authorFu, Wenxianen_US
dc.contributor.authorFarache, Juliaen_US
dc.contributor.authorClardy, Susan Men_US
dc.contributor.authorHattori, Kimieen_US
dc.contributor.authorMander, Palwinderen_US
dc.contributor.authorLee, Kevinen_US
dc.contributor.authorRioja, Inmaculadaen_US
dc.contributor.authorWeissleder, Ralphen_US
dc.contributor.authorPrinjha, Rab Ken_US
dc.contributor.authorBenoist, Christopheen_US
dc.contributor.authorMathis, Dianeen_US
dc.date.accessioned2015-02-02T15:33:19Z
dc.date.issued2014en_US
dc.identifier.citationFu, W., J. Farache, S. M. Clardy, K. Hattori, P. Mander, K. Lee, I. Rioja, et al. 2014. “Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells.” eLife 3 (1): e04631. doi:10.7554/eLife.04631. http://dx.doi.org/10.7554/eLife.04631.en
dc.identifier.issn2050-084Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13890767
dc.description.abstractEpigenetic modifiers are an emerging class of anti-tumor drugs, potent in multiple cancer contexts. Their effect on spontaneously developing autoimmune diseases has been little explored. We report that a short treatment with I-BET151, a small-molecule inhibitor of a family of bromodomain-containing transcriptional regulators, irreversibly suppressed development of type-1 diabetes in NOD mice. The inhibitor could prevent or clear insulitis, but had minimal influence on the transcriptomes of infiltrating and circulating T cells. Rather, it induced pancreatic macrophages to adopt an anti-inflammatory phenotype, impacting the NF-κB pathway in particular. I-BET151 also elicited regeneration of islet β-cells, inducing proliferation and expression of genes encoding transcription factors key to β-cell differentiation/function. The effect on β cells did not require T cell infiltration of the islets. Thus, treatment with I-BET151 achieves a ‘combination therapy’ currently advocated by many diabetes investigators, operating by a novel mechanism that coincidentally dampens islet inflammation and enhances β-cell regeneration. DOI: http://dx.doi.org/10.7554/eLife.04631.001en
dc.language.isoen_USen
dc.publishereLife Sciences Publications, Ltden
dc.relation.isversionofdoi:10.7554/eLife.04631en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270084/pdf/en
dash.licenseLAAen_US
dc.subjectautoimmune diabetesen
dc.subjectbromodomain inhibitoren
dc.subjectNF-KBen
dc.subjectmouseen
dc.titleEpigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journaleLifeen
dash.depositing.authorHattori, Kimieen_US
dc.date.available2015-02-02T15:33:19Z
dc.identifier.doi10.7554/eLife.04631*
dash.authorsorderedfalse
dash.contributor.affiliatedHattori, Kimie
dash.contributor.affiliatedMathis, Diane
dash.contributor.affiliatedBenoist, Christophe
dash.contributor.affiliatedWeissleder, Ralph


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