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
{"title":"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。","authors":"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","doi":"10.1186/s12979-025-00531-x","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"36"},"PeriodicalIF":5.6000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Early-life thymectomy results in visceral adipose tissue inflammation and glucose intolerance.\",\"authors\":\"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\",\"doi\":\"10.1186/s12979-025-00531-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":51289,\"journal\":{\"name\":\"Immunity & Ageing\",\"volume\":\"22 1\",\"pages\":\"36\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunity & Ageing\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12979-025-00531-x\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GERIATRICS & GERONTOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunity & Ageing","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12979-025-00531-x","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
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.
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.