A Guanidine-rich Regulatory Oligodeoxynucleotide Improves Type-2 Diabetes in Obese Mice by Blocking T-cell Differentiation
View/ Open
Author
Wang, Jing
Xia, Ni
Yan, Xin-Xin
Tang, Ting-Ting
Zhang, Hong-Jian
Liu, Juan
Sjöberg, Sara
Liao, Yu-Hua
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1002/emmm.201201272Metadata
Show full item recordCitation
Cheng, 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.Abstract
T 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491840/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:10589815
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)