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dc.contributor.authorCheng, Xiang
dc.contributor.authorWang, Jing
dc.contributor.authorXia, Ni
dc.contributor.authorYan, Xin-Xin
dc.contributor.authorTang, Ting-Ting
dc.contributor.authorChen, Han
dc.contributor.authorZhang, Hong-Jian
dc.contributor.authorLiu, Juan
dc.contributor.authorKong, Wen
dc.contributor.authorSjöberg, Sara
dc.contributor.authorFolco, Eduardo
dc.contributor.authorLibby, Peter
dc.contributor.authorLiao, Yu-Hua
dc.contributor.authorShi, Guo-Ping
dc.date.accessioned2013-04-26T19:51:10Z
dc.date.issued2012
dc.identifier.citationCheng, Xiang, Jing Wang, Ni Xia, Xin-Xin Yan, Ting-Ting Tang, Han Chen, Hong-Jian Zhang, et al. 2012. A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation. EMBO Molecular Medicine 4(10): 1112-1125.en_US
dc.identifier.issn1757-4676en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10589815
dc.description.abstractT lymphocytes exhibit pro-inflammatory or anti-inflammatory activities in obesity and diabetes, depending on their subtypes. Guanidine-rich immunosuppressive oligodeoxynucleotides (ODNs) effectively control Th1/Th2-cell counterbalance. This study reveals a non-toxic regulatory ODN (ODNR01) that inhibits Th1- and Th17-cell polarization by binding to STAT1/3/4 and blocking their phosphorylation without affecting Th2 and regulatory T cells. ODNR01 improves glucose tolerance and insulin sensitivity in both diet-induced obese (DIO) and genetically generated obese (ob/ob) mice. Mechanistic studies show that ODNR01 suppresses Th1- and Th17-cell differentiation in white adipose tissue, thereby reducing macrophage accumulation and M1 macrophage inflammatory molecule expression without affecting M2 macrophages. While ODNR01 shows no effect on diabetes in lymphocyte-free Rag1-deficient DIO mice, it enhances glucose tolerance and insulin sensitivity in CD4\(^+\) T-cell-reconstituted Rag1-deficient DIO mice, suggesting its beneficial effect on insulin resistance is T-cell-dependent. Therefore, regulatory ODNR01 reduces obesity-associated insulin resistance through modulation of T-cell differentiation.en_US
dc.language.isoen_USen_US
dc.publisherWILEY-VCH Verlagen_US
dc.relation.isversionofdoi:10.1002/emmm.201201272en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491840/pdf/en_US
dash.licenseLAA
dc.subjectmacrophageen_US
dc.subjectobesityen_US
dc.subjectregulatory oligodeoxynucleotideen_US
dc.subjectT-cell differentiationen_US
dc.subjecttype-2 diabetesen_US
dc.titleA Guanidine-rich Regulatory Oligodeoxynucleotide Improves Type-2 Diabetes in Obese Mice by Blocking T-cell Differentiationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalEMBO Molecular Medicineen_US
dash.depositing.authorLibby, Peter
dc.date.available2013-04-26T19:51:10Z
dc.identifier.doi10.1002/emmm.201201272*
dash.authorsorderedfalse
dash.contributor.affiliatedKong, Wen
dash.contributor.affiliatedFolco, Eduardo
dash.contributor.affiliatedCheng, Xiang
dash.contributor.affiliatedChen, Han
dash.contributor.affiliatedShi, Guo-Ping
dash.contributor.affiliatedLibby, Peter


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