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A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation

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 inhi...

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Autores principales: Cheng, Xiang, Wang, Jing, Xia, Ni, Yan, Xin-Xin, Tang, Ting-Ting, Chen, Han, Zhang, Hong-Jian, Liu, Juan, Kong, Wen, Sjöberg, Sara, Folco, Eduardo, Libby, Peter, Liao, Yu-Hua, Shi, Guo-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491840/
https://www.ncbi.nlm.nih.gov/pubmed/23027613
http://dx.doi.org/10.1002/emmm.201201272
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author Cheng, Xiang
Wang, Jing
Xia, Ni
Yan, Xin-Xin
Tang, Ting-Ting
Chen, Han
Zhang, Hong-Jian
Liu, Juan
Kong, Wen
Sjöberg, Sara
Folco, Eduardo
Libby, Peter
Liao, Yu-Hua
Shi, Guo-Ping
author_facet Cheng, Xiang
Wang, Jing
Xia, Ni
Yan, Xin-Xin
Tang, Ting-Ting
Chen, Han
Zhang, Hong-Jian
Liu, Juan
Kong, Wen
Sjöberg, Sara
Folco, Eduardo
Libby, Peter
Liao, Yu-Hua
Shi, Guo-Ping
author_sort Cheng, Xiang
collection PubMed
description 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.
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spelling pubmed-34918402012-11-09 A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation Cheng, Xiang Wang, Jing Xia, Ni Yan, Xin-Xin Tang, Ting-Ting Chen, Han Zhang, Hong-Jian Liu, Juan Kong, Wen Sjöberg, Sara Folco, Eduardo Libby, Peter Liao, Yu-Hua Shi, Guo-Ping EMBO Mol Med Research Articles 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. WILEY-VCH Verlag 2012-10 2012-10-02 /pmc/articles/PMC3491840/ /pubmed/23027613 http://dx.doi.org/10.1002/emmm.201201272 Text en Copyrights © 2012 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Research Articles
Cheng, Xiang
Wang, Jing
Xia, Ni
Yan, Xin-Xin
Tang, Ting-Ting
Chen, Han
Zhang, Hong-Jian
Liu, Juan
Kong, Wen
Sjöberg, Sara
Folco, Eduardo
Libby, Peter
Liao, Yu-Hua
Shi, Guo-Ping
A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation
title A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation
title_full A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation
title_fullStr A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation
title_full_unstemmed A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation
title_short A guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking T-cell differentiation
title_sort guanidine-rich regulatory oligodeoxynucleotide improves type-2 diabetes in obese mice by blocking t-cell differentiation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491840/
https://www.ncbi.nlm.nih.gov/pubmed/23027613
http://dx.doi.org/10.1002/emmm.201201272
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