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Largest Single-Cell Immune Study Finds 1,000+ Sex-Specific Genetic Switches

The map links baseline immune regulation to women’s greater autoimmune risk.

Overview

  • The Garvan Institute–led paper, published Thursday in The American Journal of Human Genetics, profiled more than 1.25 million circulating immune cells from 982 healthy participants.
  • Researchers used single-cell RNA sequencing and eQTL mapping, which link DNA variants to gene activity in defined cell types, to pinpoint over 1,000 switches that act differently in males and females.
  • Most of these sex-specific switches were located on autosomes, indicating sex-linked immune regulation is not confined to the X or Y chromosomes.
  • Women had higher levels of B cells and regulatory T cells with gene programs primed for inflammation, while men had more monocytes oriented toward basic maintenance tasks.
  • Female-specific variants increased expression of lupus-associated genes FCGR3A and ITGB2, reinforcing the push for sex-aware, targeted therapies over broad immunosuppression.