Objective:

To investigate sex differences in immune-cell composition, gene expression, and genetic regulation using single-cell analysis, which may have implications for understanding autoimmune diseases.

Key Findings:

• Men had higher proportions of CD14-positive monocytes, dendritic cells, natural killer cells, and various T cell types.
• Women had higher proportions of B cells, CD4-positive naive T cells, and regulatory T cells.
• 78 sex-differentially expressed genes identified, with 65 female-biased and 16 male-biased genes.
• Only 16 of the 78 genes were located on sex chromosomes, indicating autosomal regulation's role in immune sexual dimorphism.
• Female-biased genes were enriched for pathways related to tumor necrosis factor alpha signaling and interferon gamma response.
• Male-biased genes were enriched for ribosomal and RNA-processing functions.

Interpretation:

The findings suggest significant genetic regulatory associations contributing to immune differences between sexes, with implications for understanding autoimmune diseases.

Limitations:

• Study limited to participants of European ancestry, affecting generalizability across diverse populations.
• Hormonal and environmental factors not directly measured, which may influence immune responses.
• Single time-point sampling may obscure dynamic immune variations related to circadian rhythms or hormonal fluctuations.

Conclusion:

The study highlights the potential for sexually dimorphic genes to vary in immune response, emphasizing the need for further research to explore the mechanisms underlying immune diseases.