Cargando…
T-cell senescence contributes to abnormal glucose homeostasis in humans and mice
Chronic inflammation is a driving force for the development of metabolic disease including diabetes and obesity. However, the functional characteristics of T-cell senescence in the abnormal glucose homeostasis are not fully understood. We studied the patients visiting a hospital for routine health c...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416326/ https://www.ncbi.nlm.nih.gov/pubmed/30867412 http://dx.doi.org/10.1038/s41419-019-1494-4 |
_version_ | 1783403334750699520 |
---|---|
author | Yi, Hyon-Seung Kim, So Yeon Kim, Jung Tae Lee, Young-Sun Moon, Ji Sun Kim, Mingyo Kang, Yea Eun Joung, Kyong Hye Lee, Ju Hee Kim, Hyun Jin Chun, Kwangsik Shong, Minho Ku, Bon Jeong |
author_facet | Yi, Hyon-Seung Kim, So Yeon Kim, Jung Tae Lee, Young-Sun Moon, Ji Sun Kim, Mingyo Kang, Yea Eun Joung, Kyong Hye Lee, Ju Hee Kim, Hyun Jin Chun, Kwangsik Shong, Minho Ku, Bon Jeong |
author_sort | Yi, Hyon-Seung |
collection | PubMed |
description | Chronic inflammation is a driving force for the development of metabolic disease including diabetes and obesity. However, the functional characteristics of T-cell senescence in the abnormal glucose homeostasis are not fully understood. We studied the patients visiting a hospital for routine health check-ups, who were divided into two groups: normal controls and people with prediabetes. Gene expression profiling of peripheral blood mononuclear cells from normal controls and patients with type 2 diabetes was undertaken using microarray analysis. We also investigated the immunometabolic characteristics of peripheral and hepatic senescent T cells in the normal subjects and patients with prediabetes. Moreover, murine senescent T cells were tested functionally in the liver of normal or mice with metabolic deterioration caused by diet-induced obesity. Human senescent (CD28(−)CD57(+)) CD8(+) T cells are increased in the development of diabetes and proinflammatory cytokines and cytotoxic molecules are highly expressed in senescent T cells from patients with prediabetes. Moreover, we demonstrate that patients with prediabetes have higher concentrations of reactive oxygen species (ROS) in their senescent CD8(+) T cells via enhancing capacity to use glycolysis. These functional properties of senescent CD8(+) T cells contribute to the impairment of hepatic insulin sensitivity in humans. Furthermore, we found an increase of hepatic senescent T cells in mouse models of aging and diet-induced obesity. Adoptive transfer of senescent CD8(+) T cells also led to a significant deterioration in systemic abnormal glucose homeostasis, which is improved by ROS scavengers in mice. This study defines a new clinically relevant concept of T-cell senescence-mediated inflammatory responses in the pathophysiology of abnormal glucose homeostasis. We also found that T-cell senescence is associated with systemic inflammation and alters hepatic glucose homeostasis. The rational modulation of T-cell senescence would be a promising avenue for the treatment or prevention of diabetes. |
format | Online Article Text |
id | pubmed-6416326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64163262019-03-15 T-cell senescence contributes to abnormal glucose homeostasis in humans and mice Yi, Hyon-Seung Kim, So Yeon Kim, Jung Tae Lee, Young-Sun Moon, Ji Sun Kim, Mingyo Kang, Yea Eun Joung, Kyong Hye Lee, Ju Hee Kim, Hyun Jin Chun, Kwangsik Shong, Minho Ku, Bon Jeong Cell Death Dis Article Chronic inflammation is a driving force for the development of metabolic disease including diabetes and obesity. However, the functional characteristics of T-cell senescence in the abnormal glucose homeostasis are not fully understood. We studied the patients visiting a hospital for routine health check-ups, who were divided into two groups: normal controls and people with prediabetes. Gene expression profiling of peripheral blood mononuclear cells from normal controls and patients with type 2 diabetes was undertaken using microarray analysis. We also investigated the immunometabolic characteristics of peripheral and hepatic senescent T cells in the normal subjects and patients with prediabetes. Moreover, murine senescent T cells were tested functionally in the liver of normal or mice with metabolic deterioration caused by diet-induced obesity. Human senescent (CD28(−)CD57(+)) CD8(+) T cells are increased in the development of diabetes and proinflammatory cytokines and cytotoxic molecules are highly expressed in senescent T cells from patients with prediabetes. Moreover, we demonstrate that patients with prediabetes have higher concentrations of reactive oxygen species (ROS) in their senescent CD8(+) T cells via enhancing capacity to use glycolysis. These functional properties of senescent CD8(+) T cells contribute to the impairment of hepatic insulin sensitivity in humans. Furthermore, we found an increase of hepatic senescent T cells in mouse models of aging and diet-induced obesity. Adoptive transfer of senescent CD8(+) T cells also led to a significant deterioration in systemic abnormal glucose homeostasis, which is improved by ROS scavengers in mice. This study defines a new clinically relevant concept of T-cell senescence-mediated inflammatory responses in the pathophysiology of abnormal glucose homeostasis. We also found that T-cell senescence is associated with systemic inflammation and alters hepatic glucose homeostasis. The rational modulation of T-cell senescence would be a promising avenue for the treatment or prevention of diabetes. Nature Publishing Group UK 2019-03-13 /pmc/articles/PMC6416326/ /pubmed/30867412 http://dx.doi.org/10.1038/s41419-019-1494-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yi, Hyon-Seung Kim, So Yeon Kim, Jung Tae Lee, Young-Sun Moon, Ji Sun Kim, Mingyo Kang, Yea Eun Joung, Kyong Hye Lee, Ju Hee Kim, Hyun Jin Chun, Kwangsik Shong, Minho Ku, Bon Jeong T-cell senescence contributes to abnormal glucose homeostasis in humans and mice |
title | T-cell senescence contributes to abnormal glucose homeostasis in humans and mice |
title_full | T-cell senescence contributes to abnormal glucose homeostasis in humans and mice |
title_fullStr | T-cell senescence contributes to abnormal glucose homeostasis in humans and mice |
title_full_unstemmed | T-cell senescence contributes to abnormal glucose homeostasis in humans and mice |
title_short | T-cell senescence contributes to abnormal glucose homeostasis in humans and mice |
title_sort | t-cell senescence contributes to abnormal glucose homeostasis in humans and mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416326/ https://www.ncbi.nlm.nih.gov/pubmed/30867412 http://dx.doi.org/10.1038/s41419-019-1494-4 |
work_keys_str_mv | AT yihyonseung tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT kimsoyeon tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT kimjungtae tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT leeyoungsun tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT moonjisun tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT kimmingyo tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT kangyeaeun tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT joungkyonghye tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT leejuhee tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT kimhyunjin tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT chunkwangsik tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT shongminho tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice AT kubonjeong tcellsenescencecontributestoabnormalglucosehomeostasisinhumansandmice |