T-cell senescence contributes to abnormal glucose homeostasis in humans and mice
DC Field | Value | Language |
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dc.contributor.author | Yi, Hyon-Seung | - |
dc.contributor.author | Kim, So Yeon | - |
dc.contributor.author | Kim, Jung Tae | - |
dc.contributor.author | Lee, Young-Sun | - |
dc.contributor.author | Moon, Ji Sun | - |
dc.contributor.author | Kim, Mingyo | - |
dc.contributor.author | Kang, Yea Eun | - |
dc.contributor.author | Joung, Kyong Hye | - |
dc.contributor.author | Lee, Ju Hee | - |
dc.contributor.author | Kim, Hyun Jin | - |
dc.contributor.author | Chun, Kwangsik | - |
dc.contributor.author | Shong, Minho | - |
dc.contributor.author | Ku, Bon Jeong | - |
dc.date.available | 2020-11-02T06:41:11Z | - |
dc.date.issued | 2019-03 | - |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/2283 | - |
dc.description.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. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Nature Publishing Group | - |
dc.title | T-cell senescence contributes to abnormal glucose homeostasis in humans and mice | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/s41419-019-1494-4 | - |
dc.identifier.scopusid | 2-s2.0-85062869330 | - |
dc.identifier.wosid | 000462414000002 | - |
dc.identifier.bibliographicCitation | Cell Death and Disease, v.10 | - |
dc.citation.title | Cell Death and Disease | - |
dc.citation.volume | 10 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | INSULIN-RESISTANCE | - |
dc.subject.keywordPlus | ADIPOSE-TISSUE | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTOR | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | CYTOKINES | - |
dc.subject.keywordPlus | RISK | - |
dc.subject.keywordPlus | ASSOCIATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | RECEPTOR | - |
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