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T 细胞受体库的年龄相关免疫特征、胸腺近期输出功能和 microRNAs。

Age-Related Immune Profile of the T Cell Receptor Repertoire, Thymic Recent Output Function, and miRNAs.

机构信息

Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou 510632, China.

The First Affiliated Hospital, Jinan University, Guangzhou, 510632 Guangdong, China.

出版信息

Biomed Res Int. 2020 Dec 2;2020:5910823. doi: 10.1155/2020/5910823. eCollection 2020.

Abstract

BACKGROUND

T cell immunity plays a central role in the body's defense system, including maintaining homeostasis and preventing tumorigenesis and viral infection. Immune system functions degenerate with age, leading to immune senescence. Physiologically, immune senescence is characterized by a decrease in T cell receptor diversity, naive T cell deficiency, and alterations in T cell immune-related miRNAs. However, little is known about the characteristics of T cell immunosenescence in Chinese individuals.

RESULTS

A significant decrease in the miR-17, miR-92a, and miR-181a levels in PBMCs was detected with age. The miR-92a and miR-181a levels were upregulated in CBMCs when comparing healthy individuals to group I (09 years), whereas miR-17 was downregulated. The sjTREC level in PBMCs was negatively correlated with age, and a sharp decrease in sjTRECs was found between groups I and II (1019 years). Twenty-four TCR V subfamilies could be detected in most samples, and most displayed polyclonality, while skewed expression of the V subfamilies as well as an increased oligoclonal tendency was found with age. Similarly, the frequencies of the TCR V and V subfamilies decreased with age, and the alteration in clonality appeared to be stable at different ages.

CONCLUSION

We made the novel observation of T cell immunosenescence with age in Chinese individuals, which may provide information for immune targets to enhance the T cell immune response in immunotherapy settings for elderly patients.

摘要

背景

T 细胞免疫在机体防御系统中起着核心作用,包括维持体内平衡以及预防肿瘤发生和病毒感染。免疫系统功能随年龄的增长而退化,导致免疫衰老。从生理学角度来看,免疫衰老的特征是 T 细胞受体多样性减少、幼稚 T 细胞缺乏以及 T 细胞免疫相关 miRNA 改变。然而,关于中国人 T 细胞免疫衰老的特征知之甚少。

结果

随着年龄的增长,在 PBMCs 中检测到 miR-17、miR-92a 和 miR-181a 水平显著降低。与 I 组(09 岁)相比,健康个体的 CBMCs 中 miR-92a 和 miR-181a 水平上调,而 miR-17 下调。PBMCs 中的 sjTREC 水平与年龄呈负相关,并且在 I 组和 II 组(1019 岁)之间发现 sjTRECs 急剧下降。在大多数样本中可以检测到 24 个 TCR V 亚家族,并且大多数表现为多克隆性,而随着年龄的增长,V 亚家族的表达出现偏斜以及增加的寡克隆倾向。同样,TCR V 和 V 亚家族的频率随年龄的增长而降低,克隆性的改变在不同年龄似乎是稳定的。

结论

我们首次观察到中国人 T 细胞随年龄的免疫衰老,这可能为免疫治疗中增强老年患者 T 细胞免疫反应的免疫靶标提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fee7/7732372/bf4c7c012f2a/BMRI2020-5910823.001.jpg

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