Aging modulates the immunosuppressive, polarizing and metabolic functions of blood-derived myeloid-derived suppressor cells (MDSCs).

IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Emma Keltsch, Jennifer Greiner, Lena Wahl, Ingrid Knape, Daniel Tews, Michael Denkinger, Klaus-Michael Debatin, Gudrun Strauss
{"title":"Aging modulates the immunosuppressive, polarizing and metabolic functions of blood-derived myeloid-derived suppressor cells (MDSCs).","authors":"Emma Keltsch, Jennifer Greiner, Lena Wahl, Ingrid Knape, Daniel Tews, Michael Denkinger, Klaus-Michael Debatin, Gudrun Strauss","doi":"10.1186/s12979-025-00524-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immunosenescence describes the gradual remodeling of immune responses, leading to disturbed immune homeostasis and increased susceptibility of older adults for infections, neoplasia and autoimmunity. Decline in cellular immunity is associated with intrinsic changes in the T cell compartment, but can be further pushed by age-related changes in cells regulating T cell immunity. Myeloid-derived suppressor cells (MDSCs) are potent inhibitors of T cell activation and function, whose induction requires chronic inflammation. Since aging is associated with low grade inflammation (inflammaging) and increased myelopoiesis, age-induced changes in MDSC induction and function in relation to T cell immunity were analyzed.</p><p><strong>Results: </strong>MDSC numbers and functions were compared between \"healthy\" young and old adults, who were negatively diagnosed for severe acute and chronic diseases known to induce MDSC accumulation. MDSCs were either isolated from peripheral blood or generated in vitro from blood-derived CD14 cells. Aging was associated with significantly increased MDSC numbers in the monocytic- (M-) and polymorphonuclear (PMN-) MDSC subpopulations. MDSCs could be induced more efficiently from CD14 cells of old donors and these MDSCs inhibited CD3/28-induced T cell proliferation significantly better than MDSCs induced from young donors. Serum factors of old donors supported MDSC induction comparable to serum factors from young donors, but increased immunosuppressive activity of MDSCs was only achieved by serum from old donors. Elevated immunosuppressive activity of MDSCs from old donors was associated with major metabolic changes and increased intracellular levels of neutral and oxidized lipids known to promote immunosuppressive functions. Independent of age, MDSC-mediated suppression of T cell proliferation required direct MDSC- T cell contact. Besides their increased ability to inhibit activation-induced T cell proliferation, MDSCs from old donors strongly shift the immune response towards Th2 immunity and might thereby further contribute to impaired cell-mediated immunity during aging.</p><p><strong>Conclusions: </strong>These results indicate that immunosenescence of innate immunity comprises accumulation and functional changes in the MDSC compartment, which directly impacts T cell functions and contribute to age-associated impaired T cell immunity. Targeting MDSCs during aging might help to maintain functional T cell responses and increase the chance of healthy aging.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"29"},"PeriodicalIF":5.6000,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235767/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunity & Ageing","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12979-025-00524-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Immunosenescence describes the gradual remodeling of immune responses, leading to disturbed immune homeostasis and increased susceptibility of older adults for infections, neoplasia and autoimmunity. Decline in cellular immunity is associated with intrinsic changes in the T cell compartment, but can be further pushed by age-related changes in cells regulating T cell immunity. Myeloid-derived suppressor cells (MDSCs) are potent inhibitors of T cell activation and function, whose induction requires chronic inflammation. Since aging is associated with low grade inflammation (inflammaging) and increased myelopoiesis, age-induced changes in MDSC induction and function in relation to T cell immunity were analyzed.

Results: MDSC numbers and functions were compared between "healthy" young and old adults, who were negatively diagnosed for severe acute and chronic diseases known to induce MDSC accumulation. MDSCs were either isolated from peripheral blood or generated in vitro from blood-derived CD14 cells. Aging was associated with significantly increased MDSC numbers in the monocytic- (M-) and polymorphonuclear (PMN-) MDSC subpopulations. MDSCs could be induced more efficiently from CD14 cells of old donors and these MDSCs inhibited CD3/28-induced T cell proliferation significantly better than MDSCs induced from young donors. Serum factors of old donors supported MDSC induction comparable to serum factors from young donors, but increased immunosuppressive activity of MDSCs was only achieved by serum from old donors. Elevated immunosuppressive activity of MDSCs from old donors was associated with major metabolic changes and increased intracellular levels of neutral and oxidized lipids known to promote immunosuppressive functions. Independent of age, MDSC-mediated suppression of T cell proliferation required direct MDSC- T cell contact. Besides their increased ability to inhibit activation-induced T cell proliferation, MDSCs from old donors strongly shift the immune response towards Th2 immunity and might thereby further contribute to impaired cell-mediated immunity during aging.

Conclusions: These results indicate that immunosenescence of innate immunity comprises accumulation and functional changes in the MDSC compartment, which directly impacts T cell functions and contribute to age-associated impaired T cell immunity. Targeting MDSCs during aging might help to maintain functional T cell responses and increase the chance of healthy aging.

衰老调节血源性髓源性抑制细胞(MDSCs)的免疫抑制、极化和代谢功能。
背景:免疫衰老描述了免疫反应的逐渐重塑,导致免疫稳态紊乱,老年人对感染、肿瘤和自身免疫的易感性增加。细胞免疫力的下降与T细胞区室的内在变化有关,但可以进一步被调节T细胞免疫的细胞的年龄相关变化所推动。髓源性抑制细胞(MDSCs)是T细胞激活和功能的有效抑制剂,其诱导需要慢性炎症。由于衰老与低度炎症(炎症)和骨髓生成增加有关,因此分析了年龄诱导的MDSC诱导和功能变化与T细胞免疫的关系。结果:比较了“健康”年轻人和老年人MDSC的数量和功能,这些人被诊断患有已知可诱导MDSC积累的严重急性和慢性疾病。MDSCs可以从外周血中分离,也可以从血液来源的CD14细胞中体外生成。在单核- (M-)和多形核(PMN-) MDSC亚群中,衰老与MDSC数量显著增加有关。老年供者的CD14细胞可以更有效地诱导MDSCs,并且这些MDSCs对cd3 /28诱导的T细胞增殖的抑制作用明显优于年轻供者的MDSCs。与年轻供者的血清因子相比,老年供者的血清因子支持MDSCs的诱导,但MDSCs的免疫抑制活性仅由老年供者的血清实现。老年供体MDSCs免疫抑制活性的升高与主要代谢变化和细胞内中性和氧化脂质水平的增加有关,这些脂质已知可促进免疫抑制功能。与年龄无关,MDSC介导的T细胞增殖抑制需要MDSC- T细胞直接接触。除了抑制激活诱导的T细胞增殖的能力增强外,来自老年供体的MDSCs强烈地将免疫反应转向Th2免疫,从而可能进一步导致衰老过程中细胞介导的免疫受损。结论:这些结果表明,先天免疫的免疫衰老包括MDSC室的积累和功能改变,直接影响T细胞功能,并导致与年龄相关的T细胞免疫功能受损。在衰老过程中靶向MDSCs可能有助于维持功能性T细胞反应并增加健康衰老的机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信