Researchers have uncovered how hormones profoundly affect our immune systems, explaining why men and women are affected by diseases differently.
By LMS Staff Member
September 4, 2024
Time to read: 5 minutes
Immunologist, Professor Petter Brodin, now working at the Laboratory of Medical Sciences and Imperial College London has published ground breaking work which shines new light on sex-based differences in health. This work could provide insights into future treatments of medical conditions which can affect males and females differently. The research has explored which aspects of our immune systems are regulated by sex hormones, and the impact this has on disease risk and health outcomes.
Many diseases affect men and women differently, due to subtle differences in our immune systems. For example, some auto-immune conditions, such as systemic lupus erythematosus (SLE) are found much more commonly in females, whereas some conditions, such as COVID-19, conferred a greater risk acute first-time infections in males, with females have a greater risk of long-COVID. Until now it has proved difficult to unpick the interplay and influence of genetics, hormones and behaviour on our immune systems; which elements are affected; and how this influences subsequent disease risk.
Today’s newly published clinical study, carried out at the Karolinksa Institute in Sweden, involved 23 transgender men receiving hormone therapy, following them over time to monitor how their immune systems changed as a result of the hormones. Researchers have now been able to begin to untangle which elements of the immune system are dynamically regulated by sex hormones, from elements assigned by genetics – research that sheds new light on why males and females tend to have different responses to immunological challenges which results in differing susceptibility to different disease conditions.
The findings have shown that increased testosterone and reduced oestrogen levels alter the balance between two crucial immune signalling systems that have direct implications for how we respond to infection and disease: antiviral interferon type 1 (IFN-1) and proinflammatory signals such as tumour necrosis factor alpha (TNF-α).According to the researchers, the findings – published today in the journal Nature – help to explain, for the first time, the mechanisms that underpin differences in the risk of infections, autoimmune diseases, and cancers among males and females, but could also open up potential avenues for new, more targeted treatments. They add that the work also highlights the importance of ensuring long-term clinical follow ups for trans individuals undergoing hormone therapy, and the long-term impacts that treatment may have on their immune system and disease risk.
Professor Petter Brodin, Garfield Weston Chair and Professor of Paediatric immunology at Imperial College London, who led the work while based at the Karolinska Institutet, said:
“These findings have implications for us all. For the first time, we have been able to identify which parts of a person’s immune system are directly regulated by sex hormones rather than genetic sex differences. This could have significant impact not only on our understanding of how different diseases affect males and females differently, but also to develop new treatments which could help in everything from immune diseases to cancer.”
In the latest study, clinical researchers at the Karolinska Institute recruited 23 transgender men, who had been registered ‘female’ at birth and were undergoing testosterone treatment. The team collected blood samples from patients before treatment, and then following three months and one year of testosterone treatment, analysing differences in the immune cells and proteins in the blood.
Analysis revealed several key elements of the immune system that changed following treatment, including pathways for inflammatory responses to infections and disease. Among these were TNF-α and IFN-1, which play critical roles in inflammation, recognising microbial invaders, and modulating immune responses to damage, disease and threats.
To test whether the observed changes were directly due to the increase in testosterone or indirectly from reduced oestrogen, the team analysed blood from 11 female donors. Samples were treated with receptor blockers to show that the effect was directly due to testosterone signalling, rather than loss of oestradiol-signaling.
According to the researchers, the findings are important for understanding direct immunological consequences of hormone therapy in trans people. They add that changes to immune regulatory elements seen with hormone therapy may also explain why men and women respond differently to infections, and why males are more likely to experience ‘cytokine storms’ and increased mortality risk over females with COVID-19 and other severe infections.