Testosterone regulation of human immunity

Immune-mediated diseases exhibit marked sex bias.

Although men present with more severe infections and have lower vaccine responses, treatment strategies still neglect biological sex. The mechanisms underlying immune sexual dimorphism are still widely unknown.

Here I propose three aims that combine unique cohorts, high throughput multiomics and innovative computational methods to investigate testosterone regulation of human immunity.

The first aim we will investigate immunity in the context of increased testosterone signaling in women with polycystic ovary syndrome.

The second aim will investigate the impact of testosterone signaling inhibition on antitumor and antiviral immune responses in cohorts of prostate cancer and COVID-19.

The third aim will apply in vitro mechanistic experimentation to investigate the role of the testosterone receptor in immune cell transcriptional regulation and functional responses.

By employing systems-level immunoprofiling methodologies we will be able to address testosterone regulation of the immune system as a network of interacting factors and cells.

Overall, this proposal will require four years of research, and will converge on identifying testosterone-regulated pathways in immunity, defining yet untapped targets for immune intervention.

Considering sex-specific immune responses in treatment strategies has the potential to bridge existing gaps in disease management, paving the way for more tailored and effective therapeutic approaches.