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衰老对小鼠胸腺中不变自然杀伤 T 细胞表型的影响。

Impact of Aging on the Phenotype of Invariant Natural Killer T Cells in Mouse Thymus.

机构信息

Institute of Immunology, Hannover Medical School, Hannover, Germany.

Research Core Unit Genomics, Hannover Medical School, Hannover, Germany.

出版信息

Front Immunol. 2020 Oct 30;11:575764. doi: 10.3389/fimmu.2020.575764. eCollection 2020.

DOI:10.3389/fimmu.2020.575764
PMID:33193368
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7662090/
Abstract

Invariant natural killer T (iNKT) cells represent a subclass of T cells possessing a restricted repertoire of T cell receptors enabling them to recognize lipid derived ligands. iNKT cells are continuously generated in thymus and differentiate into three main subpopulations: iNKT1, iNKT2, and iNKT17 cells. We investigated the transcriptomes of these subsets comparing cells isolated from young adult (6-10 weeks old) and aged BALB/c mice (25-30 weeks of age) in order to identify genes subject to an age-related regulation of expression. These time points were selected to take into consideration the consequences of thymic involution that radically alter the existing micro-milieu. Significant differences were detected in the expression of histone genes affecting all iNKT subsets. Also the proliferative capacity of iNKT cells decreased substantially upon aging. Several genes were identified as possible candidates causing significant age-dependent changes in iNKT cell generation and/or function such as genes coding for granzyme A, ZO-1, EZH2, SOX4, IGF1 receptor, FLT4, and CD25. Moreover, we provide evidence that IL2 differentially affects homeostasis of iNKT subsets with iNKT17 cells engaging a unique mechanism to respond to IL2 by initiating a slow rate of proliferation.

摘要

固有自然杀伤 T(iNKT)细胞是 T 细胞的一个亚类，其 T 细胞受体具有有限的多样性，使其能够识别脂质衍生的配体。iNKT 细胞在胸腺中不断产生，并分化为三个主要亚群：iNKT1、iNKT2 和 iNKT17 细胞。为了鉴定受年龄相关表达调控的基因，我们比较了从小鼠（6-10 周龄）和老年 BALB/c 小鼠（25-30 周龄）胸腺中分离的这些亚群的转录组。选择这些时间点是为了考虑到胸腺萎缩对现有微环境的影响。在影响所有 iNKT 亚群的组蛋白基因表达方面检测到显著差异。此外，iNKT 细胞的增殖能力随着年龄的增长而显著下降。一些基因被鉴定为可能的候选基因，它们导致 iNKT 细胞生成和/或功能的显著年龄依赖性变化，例如编码颗粒酶 A、ZO-1、EZH2、SOX4、IGF1 受体、FLT4 和 CD25 的基因。此外，我们提供的证据表明，IL2 以不同的方式影响 iNKT 亚群的稳态，iNKT17 细胞通过启动缓慢的增殖来响应 IL2 的独特机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d2/7662090/02a06498ffdc/fimmu-11-575764-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d2/7662090/5ecc6e42ddec/fimmu-11-575764-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d2/7662090/ee0cef32ec96/fimmu-11-575764-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d2/7662090/e17fa64d2133/fimmu-11-575764-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d2/7662090/02a06498ffdc/fimmu-11-575764-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d2/7662090/5ecc6e42ddec/fimmu-11-575764-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d2/7662090/ee0cef32ec96/fimmu-11-575764-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d2/7662090/e17fa64d2133/fimmu-11-575764-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d2/7662090/02a06498ffdc/fimmu-11-575764-g004.jpg

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