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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
WILEY-VCH Verlag
2012
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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. |
format | Online Article Text |
id | pubmed-3491840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | WILEY-VCH Verlag |
record_format | MEDLINE/PubMed |
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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