Amazing stuff!
"... Now, researchers have discovered over 1,000 genetic switches that operate differently in female and male immune cells, driving higher overall activity of inflammatory pathways in females. ...
Advances in single-cell technologies now allow researchers to study individual immune cells in great detail. This study is the first to examine immunity differences between males and females at single-cell resolution on this scale.
The team sequenced over 1.25 million peripheral blood mononuclear cells – immune cells circulating in the blood – from nearly 1,000 healthy individuals. ... These participants were part of the OneK1K cohort, a major Australian project designed to map how genetics influence individual immune cells at a population scale.
The analysis revealed distinct cellular profiles between the sexes.
Males had higher proportions of monocytes, cells that act as first immune responders, and their genetic activity was more concentrated on basic cellular maintenance and protein-building functions.
In contrast, females possessed higher levels of immune cells called B cells and regulatory T cells, with genetic activity heavily skewed towards inflammatory pathways.
“While this highly reactive immune profile gives females an advantage in fighting viral infections, it comes with a biological trade-off: a greater predisposition to autoimmune diseases. On the other hand, male immune cells are less primed for inflammation, making men generally more susceptible to infections and non-reproductive cancers,” ..."
From the abstract:
"Sex has a key role in disease susceptibility (in particular, autoimmunity).
Sex differences in the immune system originate from genes and their interactions with both intrinsic and extrinsic factors.
However, the cellular-level factors influencing sexual dimorphism are not fully understood.
We thus examined immune sex differences at single-cell resolution to dissect the genetic impacts.
Female-biased sex-differentially expressed genes (sex-DEGs) in multiple immune cells were involved in tumor necrosis factor alpha (TNF-α) signaling, whereas
male DEGs were enriched for ribosomal-related functions.
While cis-expression trait quantitative loci (eQTLs) were less common on sex chromosomes, we identified over 1,000 sex-specific eQTLs and 51 sex-interacting eQTLs on autosomes.
When we examined the effect of genetic control on sex-DEGs, we found genetic variants affecting the female-biased expression of FCGR3A in natural killer (NK) cells (rs2099684) and ITGB2 in monocytes (rs760462), both of which are associated with systemic lupus erythematosus.
Our work reveals biases masked in bulk analyses and highlights sexually dimorphic genes and pathways at baseline."
Figure 1 Overview of study
Figure 2 Distributions of cell-type proportions across sex
Figure 3 Sex-differential expression
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