Brace yourselves. Scientists from the Karolinska Institutet in Sweden and Imperial College London have shown for the first time which aspects of our immune systems are regulated by sex hormones, and the impacts this has on disease risk and health outcomes in males and females.
Researchers recruited 23 transgender men and 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.
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.
Sex hormones modulate the immune system to influence disease risk differently | Imperial News | Imperial College London
We performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals.
Immune system adaptation during gender-affirming testosterone treatment | Nature