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单细胞分析衰老卵巢免疫系统揭示了向适应性免疫的转变和细胞功能的减弱。

Single-cell analysis of the aged ovarian immune system reveals a shift towards adaptive immunity and attenuated cell function.

机构信息

Department of Physiology, Biophysics and Systems Biology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.

Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel.

出版信息

Elife. 2023 Apr 25;12:e74915. doi: 10.7554/eLife.74915.

DOI:10.7554/eLife.74915
PMID:37096871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10188116/
Abstract

The immune system plays a major role in maintaining many physiological processes in the reproductive system. However, a complete characterization of the immune milieu in the ovary, and particularly how it is affected by female aging, is still lacking. Here, we utilize single-cell RNA sequencing and flow cytometry to construct the complete description of the murine ovarian immune system. We show that the composition of the immune cells undergoes an extensive shift with age towards adaptive immunity. We analyze the effect of aging on gene expression and chemokine and cytokine networks and show an overall decreased expression of inflammatory mediators together with an increased expression of senescent cells recognition receptors. Our results suggest that the fertile female's ovarian immune aging differs from the suggested female post-menopause inflammaging as it copes with the inflammatory stimulations during repeated cycles and the increasing need for clearance of accumulating atretic follicles.

摘要

免疫系统在维持生殖系统的许多生理过程中起着重要作用。然而,卵巢中免疫环境的完整特征,特别是其如何受到女性衰老的影响,仍然缺乏研究。在这里,我们利用单细胞 RNA 测序和流式细胞术构建了完整的小鼠卵巢免疫系统描述。我们表明,免疫细胞的组成随着年龄的增长而发生广泛的转变,向适应性免疫转变。我们分析了衰老对基因表达和趋化因子及细胞因子网络的影响,结果表明炎症介质的总体表达降低,同时衰老细胞识别受体的表达增加。我们的研究结果表明,生育期女性的卵巢免疫衰老与绝经后女性的炎症衰老不同,因为前者需要应对反复周期中的炎症刺激以及不断增加的清除堆积的闭锁卵泡的需求。

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