More than 1,000 genetic switches reveal why female immunity is different
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- Garvan Institute and UNSW researchers identified more than 1,000 sex-specific genetic switches in immune cells, with most located on non-sex chromosomes rather than the X and Y chromosomes scientists had long assumed drove sex-based immune differences
- The team sequenced more than 1.25 million individual immune cells from nearly 1,000 healthy participants in the OneK1K cohort, marking the first large-scale single-cell study of male-female immune differences
- Female immune cells showed greater numbers of B cells and regulatory T cells, with genetic activity heavily concentrated in inflammatory pathways, while male cells had more monocytes focused on basic cell maintenance and protein production
- Two genes linked to systemic lupus erythematosus displayed female-biased expression patterns, potentially explaining why lupus strikes roughly nine women for every one man
- The study, published in The American Journal of Human Genetics, provides a genetic layer of evidence that the one-size-fits-all approach to autoimmune treatment may be inadequate and could pave the way for sex-tailored therapies
- Dr. Sara Ballouz said females' highly reactive immune profile offers an advantage against viral infections but creates a biological trade-off of greater autoimmune susceptibility, while men's less-primed inflammatory response makes them more vulnerable to infections and non-reproductive cancers
Why it matters: Autoimmune diseases like lupus strike women roughly 9-to-1 over men, yet most treatments broadly suppress the immune system. By mapping 1,000+ sex-specific genetic controls, this study gives drug developers concrete biological targets for sex-tailored therapies and a long-missing genetic justification for why current one-size-fits-all autoimmune treatments have underperformed in women.
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