T-cell senescence contributes to abnormal glucose homeostasis in humans and mice

Hyon Seung Yi, So Yeon Kim, Jung Tae Kim, Young-Sun Lee, Ji Sun Moon, Mingyo Kim, Yea Eun Kang, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Kwangsik Chun, Minho Shong, Bon Jeong Ku

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 (CD28CD57+) 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.

Original languageEnglish
Article number249
JournalCell Death and Disease
Volume10
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

Fingerprint

Cell Aging
Homeostasis
T-Lymphocytes
Glucose
Prediabetic State
Liver
Obesity
Reactive Oxygen Species
Diet
Inflammation
Adoptive Transfer
Metabolic Diseases
Gene Expression Profiling
Glycolysis
Microarray Analysis
Type 2 Diabetes Mellitus
Insulin Resistance
Blood Cells
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

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.

In: Cell Death and Disease, Vol. 10, No. 3, 249, 01.03.2019.

Research output: Contribution to journalArticle

Yi, HS, Kim, SY, Kim, JT, Lee, Y-S, Moon, JS, Kim, M, Kang, YE, Joung, KH, Lee, JH, Kim, HJ, Chun, K, Shong, M & Ku, BJ 2019, 'T-cell senescence contributes to abnormal glucose homeostasis in humans and mice', Cell Death and Disease, vol. 10, no. 3, 249. https://doi.org/10.1038/s41419-019-1494-4
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. In: Cell Death and Disease. 2019 ; Vol. 10, No. 3.
@article{4cc449e9e2e84d7188cf7f00d58b83a1,
title = "T-cell senescence contributes to abnormal glucose homeostasis in humans and mice",
abstract = "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.",
author = "Yi, {Hyon Seung} and Kim, {So Yeon} and Kim, {Jung Tae} and Young-Sun Lee and Moon, {Ji Sun} and Mingyo Kim and Kang, {Yea Eun} and Joung, {Kyong Hye} and Lee, {Ju Hee} and Kim, {Hyun Jin} and Kwangsik Chun and Minho Shong and Ku, {Bon Jeong}",
year = "2019",
month = "3",
day = "1",
doi = "10.1038/s41419-019-1494-4",
language = "English",
volume = "10",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - T-cell senescence contributes to abnormal glucose homeostasis in humans and mice

AU - Yi, Hyon Seung

AU - Kim, So Yeon

AU - Kim, Jung Tae

AU - Lee, Young-Sun

AU - Moon, Ji Sun

AU - Kim, Mingyo

AU - Kang, Yea Eun

AU - Joung, Kyong Hye

AU - Lee, Ju Hee

AU - Kim, Hyun Jin

AU - Chun, Kwangsik

AU - Shong, Minho

AU - Ku, Bon Jeong

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85062869330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062869330&partnerID=8YFLogxK

U2 - 10.1038/s41419-019-1494-4

DO - 10.1038/s41419-019-1494-4

M3 - Article

C2 - 30867412

AN - SCOPUS:85062869330

VL - 10

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 3

M1 - 249

ER -