Back

The impact of sex on the immune system explored at the single-cell level

Yazar, S.; Alquicira-Hernandez, J.; Wing, K.; Senabouth, A.; Andersen, S.; Fairfax, K. A.; Hewitt, A. W.; Powell, J. E.; Ballouz, S.

2025-07-31 immunology
10.1101/2025.07.27.667062 bioRxiv
Show abstract

Sex has a key role in disease susceptibility, in particular autoimmunity. Sex differences of the immune system stems from genes and their interactions with intrinsic and external factors. However, the cellular-level factors influencing sexual dimorphism is not fully understood. We thus examined immune sex differences at single-cell resolution to dissect the genetic impacts. Female-biased sex-differentially expressed genes (DEGs) in multiple immune cells were involved in TNF[a] signalling, whereas male DEGs were enriched for ribosomal-related functions. While cis-eQTLs were less common on sex chromosomes, we identified over 1000 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 FCGR3A in NK cells (rs2099684) and ITGB2 in Monocytes (rs760462), both of which are associated with systemic lupus erythematosus. Our work reveals novel biases masked in bulk analyses and highlights sexually dimorphic genes and pathways at baseline.

Published in The American Journal of Human Genetics · training set

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

1
eLife
● 5828 papers in training set
Top 0.9%
30.1%
Similar papers in this journal
2
Cell Reports
○ 1498 papers in training set
Top 1%
11.5%
Similar papers in this journal
3
Genome Research
● 468 papers in training set
Top 0.5%
9.5%
Similar papers in this journal
50% of probability mass above
4
Cell Genomics
○ 172 papers in training set
Top 0.6%
6.5%
Similar papers in this journal
5
Nature Communications
○ 5641 papers in training set
Top 24%
6.5%
Similar papers in this journal
6
Communications Biology
○ 993 papers in training set
Top 6%
3.1%
7
Life Science Alliance
● 285 papers in training set
Top 1%
3.1%
8
iScience
○ 1154 papers in training set
Top 8%
3.1%
9
Frontiers in Immunology
○ 638 papers in training set
Top 4%
2.7%
10
Cell
○ 431 papers in training set
Top 5%
2.3%
11
Science Advances
● 1243 papers in training set
Top 17%
2.1%
12
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 29%
1.6%
13
Development
● 497 papers in training set
Top 4%
1.3%
14
Scientific Reports
○ 3612 papers in training set
Top 66%
1.1%
15
BMC Biology
○ 265 papers in training set
Top 5%
1.0%
16
Molecular Ecology
○ 336 papers in training set
Top 4%
0.8%
17
PLOS Biology
● 486 papers in training set
Top 12%
0.8%
18
BMC Genomics
○ 406 papers in training set
Top 8%
0.8%
19
Nucleic Acids Research
◐ 1281 papers in training set
Top 14%
0.8%
20
PLOS Genetics
● 862 papers in training set
Top 12%
0.8%
21
Genome Biology
○ 637 papers in training set
Top 10%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.