Source: Zhongshan Ophthalmic Center
Edited by: Tan Rongyu, Wang Dongmei

Recently, the research teams of Prof. Wenru Su and Prof. Yingfeng Zheng from Zhongshan Ophthalmic Center, Sun Yat-sen University co-published their latest research entitled “Effects of sex and aging on the immune cell landscape as assessed by single-cell transcriptomic analysis” in Proc Natl Acad Sci U S A. This work expands our knowledge of sex differences in the immune system in humans.

Sex and aging are biological variables that influence immune system composition, development, and the repertoire of responses to pathogenic insults. The type and severity of immune disorders differ greatly between males and females. Additionally, sex-based differences in the responses to many vaccines have been reported for adults. Females are generally more susceptible to experiencing adverse side effects from vaccinations and generate more antibodies than males. Sex and aging affect the composition of the immune microenvironment, thereby contributing to sex-based differences in the response to infection and development of autoimmune disease and cancer. A comprehensive immune cell atlas that encompasses the influences of sex and aging at a single-cell resolution is needed to reveal how the immune system integrates numerous interconnected components, pathways, and cell types in sex and aging.

In this study, the team conducted single-cell RNA sequencing to analyze the transcriptomes of peripheral blood mononuclear cells (PBMCs) from volunteers of different ages and sexes. The single immune cell profiling of PBMCs was accurately mapped at the single cell resolution by comparing the proportion of cell subsets, functional analysis of differential expressed genes (DEGs), and analysis of cell-cell communication (FIG. 1).

This study found that females had a lower percentage of NK cells and a higher percentage of plasma cells in PBMCs compared to males. Bioinformatics revealed that young females exhibited an overrepresentation of pathways that relate to T and B cell activation. Moreover, cell-cell communication analysis revealed evidence of increased activity of the BAFF/APRIL systems in females. Notably, aging increased the percentage of monocytes and reduced the percentage of na?ve T cells in the blood, and the number of DEGs between the sexes. Aged males expressed higher levels of inflammatory genes. These findings might aid in the understanding of the mechanisms underlying sex-based differences in immunity and disease-susceptibility across the lifespan and provide a new direction for exploring the potential significance and influence of sex and aging in the pathogenesis of ocular immune diseases such as Behcet's disease.

This study was supported by the National Key R&D Program of China (2017YFA0105804).

Link to the paper: https://www.pnas.org/content/118/33/e2023216118