早期胸腺切除术导致内脏脂肪组织炎症和葡萄糖耐受不良。

IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY
David J Buckley, Sogol Zahedi, Prema Velusamy, Sunita Sharma, Manoj Sabnani, Lisa C Flores, Ganga Tandukar, Yuji Ikeno, Paul J Fadel, Lisa A Lesniewski, Daniel W Trott
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引用次数: 0

摘要

我们之前已经证明,脂肪组织和肝脏中的促炎T细胞在老年小鼠的葡萄糖耐受不良中起机制作用。此外,我们和其他人已经证明,在年轻健康的小鼠中,早期胸腺切除术导致的T细胞表型与经典T细胞衰老的许多特征相同。在这项研究中,我们试图验证一种假设,即通过早期胸腺切除术诱导过早的T细胞衰老会导致T细胞介导的肝脏和内脏脂肪组织炎症,以及其他年轻小鼠的葡萄糖耐受不良。小鼠在三周龄时切除胸腺。在9个月大时,去胸腺的小鼠表现出与体重无关的葡萄糖耐受不良,并且更加虚弱。去胸腺小鼠在脾脏、肝脏和耻骨周围脂肪组织(pgWAT)中表现出naïve比例钝化和更大比例的记忆细胞。pgWAT的大量RNAseq显示,胸腺去甲基化小鼠表现出负责免疫激活、趋化因子信号和炎症的基因上调,以及负责代谢功能的基因下调。我们还发现,胸腺去角质小鼠pgWAT中的T细胞表现出更高的趋化因子受体表达,以及与更大的脂肪组织扩张无关的组织病理学炎症标志物的增加。这些结果表明,早期胸腺切除术会导致成年小鼠T细胞介导的pgWAT炎症、全身葡萄糖耐受不良和虚弱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Early-life thymectomy results in visceral adipose tissue inflammation and glucose intolerance.

We have previously demonstrated that proinflammatory T cells in adipose tissue and the liver play a mechanistic role in glucose intolerance in old mice. Further, we and others have demonstrated that early life thymectomy results in a T cell phenotype that shares many features of classical T cell aging in an otherwise young healthy mouse. In this investigation, we sought to test the hypothesis that inducing premature T cell aging via early life thymectomy results in T cell mediated inflammation of the liver and visceral adipose tissue, as well as glucose intolerance in otherwise young mice. Mice were thymectomized at three weeks of age. At 9 months of age, thymectomized mice exhibited glucose intolerance that was independent of body mass along with greater frailty. Thymectomized mice exhibited blunted proportions of naïve and greater proportions of memory cells in the spleen, liver and perigonadal adipose tissue (pgWAT). Bulk RNAseq of the pgWAT revealed that thymectomized mice exhibited an upregulation of genes responsible for immune activation, chemokine signaling, and inflammation along with a downregulation of genes responsible for metabolic function. We also found that T cells in the pgWAT of thymectomized mice exhibited greater chemokine receptor expression as well as increased markers of histopathological inflammation that were independent of greater adipose tissue expansion. These results suggest that early life thymectomy results in T cell mediated pgWAT inflammation, systemic glucose intolerance and frailty in adult mice.

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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
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