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

With aging, the immune system undergoes immunosenescence, accompanied by chronic low-grade inflammation (inflammaging). Balanced immunity relies on effector and regulatory cells, with myeloid-derived suppressor cells (MDSCs) playing a key regulatory role. MDSCs, a heterogeneous population of immature myeloid cells, develop under inflammatory conditions and primarily suppress T cell activity. The age-dependent increase in myelopoiesis and inflammation, along with reduced immune reactivity, suggests that changes in the number and function of regulatory cells, such as MDSCs, might strongly contribute to age-related modifications of immune responses. While studies in mice have demonstrated an age-related increase in MDSC numbers, human studies have predominantly focused on cancer patients, making it challenging to separate the effects of aging and cancer on MDSC induction. Therefore, we analyzed MDSC increases in older individuals without a history of cancer. Furthermore, we excluded patients with neurodegenerative, cardiovascular or autoimmune diseases. We found a significant increase in circulating MDSCs in old donors. In addition, in vitro generated, blood-derived MDSCs from old donors exhibited enhanced immunosuppressive and Th2 polarizing capacity. RNA sequencing indicated age-related metabolic changes. These findings highlight that age-related changes in MDSCs contribute to dysregulated immune functions during aging. This study investigates age-related transcriptional changes in isolated CD14+ and CD14+-derived MDSCs (myeloid-derived suppressor cells) using RNA-seq. Blood was collected from young (20-35 years) and old (70+ years) donors. CD14+ cells from each donor were isolated and used for RNA isolation and/or in vitro-induction of MDSCs. The dataset consists of 7 RNA-seq samples from CD14+ cells (3 young, 4 old) and 9 from CD14+-derived MDSCs (4 young, 5 old). The goal is to assess age-related transcriptional changes within CD14+ cells, differentiated MDSCs, and during the monocyte-to-MDSC differentiation process.

随着衰老进程，免疫系统会发生免疫衰老（immunosenescence），并伴随慢性低度炎症状态，即炎性衰老（inflammaging）。机体免疫稳态依赖于效应细胞与调节细胞的协同平衡，其中髓系来源抑制细胞（myeloid-derived suppressor cells，MDSCs）发挥着关键的调控作用。MDSCs是一类异质性未成熟髓系细胞群体，在炎症条件下分化产生，其核心功能为抑制T细胞活性。随年龄增长出现的髓系生成增强、炎症水平升高，以及免疫反应性降低，提示以MDSCs为代表的调节细胞的数量与功能改变，可能极大地参与了衰老相关的免疫应答异常。尽管小鼠研究已证实MDSC数量随年龄增长而升高，但针对人类的相关研究多聚焦于癌症患者，因此难以区分衰老与癌症对MDSC诱导的影响。为此，本研究分析了无癌症病史的老年个体体内MDSC的升高情况，并排除了患有神经退行性疾病、心血管疾病或自身免疫性疾病的受试者。研究结果显示，老年供者的循环MDSC数量显著升高。此外，体外诱导生成的、源自老年供者血液的MDSCs，其免疫抑制与Th2极化能力均显著增强。RNA测序结果揭示了衰老相关的代谢改变。上述发现表明，MDSCs的衰老相关变化会导致衰老过程中免疫功能失调。本研究借助RNA测序技术，探究了分离得到的CD14+细胞以及CD14+细胞来源的髓系来源抑制细胞（MDSCs）中的衰老相关转录组变化。研究采集了年轻（20~35岁）与老年（70岁及以上）供者的外周血。从每名供者体内分离CD14+细胞，用于RNA提取以及/或体外诱导MDSCs。本数据集包含7份CD14+细胞的RNA-seq样本（3份来自年轻供者，4份来自老年供者）以及9份CD14+细胞来源MDSCs的RNA-seq样本（4份来自年轻供者，5份来自老年供者）。本研究的目标为评估CD14+细胞、分化成熟的MDSCs，以及单核细胞向MDSCs分化过程中，与衰老相关的转录组变化。