Hormones and Gender Differences in Immune Response

Scientists have discovered that hormones have a tremendous impact on our immune systems, which helps to explain why diseases affect men and women differently.

For the first time, researchers from Imperial College London and the Karolinska Institutet in Sweden have demonstrated which components of our immune systems are influenced by sex hormones and the effects this has on both male and female health outcomes and illness risk.

It is often known that due to minute variations in our immune systems, illnesses might affect men and women differently. For instance, women are nine times more likely to suffer from systemic lupus erythematosus (SLE), and when it comes to COVID-19, males are known to be more likely to contract acute first-time infections while females are more likely to contract long-term infections.

Determining which components of our immune systems are impacted by our genetics, hormones, and behavior, as well as how this affects the risk of disease in the future, has proven to be challenging.

It has now been possible to distinguish between the components of the immune system that are genetically assigned and those that are dynamically influenced by sex hormones in a clinical investigation including twenty-three transgender individuals undergoing hormone therapy.

The results show how altered levels of testosterone and decreased oestrogen affect the balance between two immune signaling systems that are important for the immune system’s response to illness and infection: proinflammatory signals like TNF-α and the antiviral interferon type 1 (IFN-1).

The results, which were published today in the journal Nature, not only help to explain the mechanisms underlying the differences between males and females’ susceptibilities to infections, autoimmune diseases, and cancers for the first time, but they may also pave the way for the development of novel, more focused treatments.

They continue by saying that the research also emphasizes how crucial it is to guarantee trans people receiving hormone therapy long-term clinical follow-ups, as well as the potential long-term effects of the medication on immune function and illness 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.”

Treatment for testosterone
The most recent study involved the recruitment of 23 transgender guys who were receiving testosterone medication and had been registered as “female” at birth by clinical researchers at the Karolinska Institutet. Before, during, and after three months and a year of testosterone treatment, the patients’ blood samples were obtained by the researchers, who then analyzed the variations in the immune cells and proteins in the blood.

Analysis showed that the immune system underwent changes in a number of important areas after treatment, including the pathways governing inflammatory reactions to infections and illnesses. These included TNF-α and IFN-1, which are essential for inflammation, identifying microbial invaders, and adjusting immune responses to illness, injury, and danger.

The researchers examined blood from 11 female donors to determine if the observed alterations were caused directly by an increase in testosterone or indirectly by a decrease in oestrogen. Receptor blockers were applied to the samples to demonstrate that the effect was caused by testosterone signaling and not by oestradiol signaling decline.

The findings, according to the researchers, are critical to comprehending the direct immunological effects of hormone therapy on transgender individuals. Men and women react to infections differently, and men are more likely than females to have “cytokine storms” and a higher risk of death from COVID-19 and other serious infections. They also note that changes to immune regulatory components observed with hormone therapy may help explain these differences.

Recognizing the disparities in sex
At Imperial’s Hammersmith Campus, the Medical Research Council Laboratory for Medical Science (MRC LMS) is where Professor Brodin is currently carrying out the remaining work. Blood samples will be analyzed in more research to determine which immune system components and pathways might be the focus of treatment.

Professor Brodin added: “We’re extremely grateful to the people who contributed to this study. Trans individuals are a hugely under-represented and under-served group in medicine. In addition to the invaluable immunological insights we’ve uncovered here, the involvement of this small group of people will enable us to gain deeper insights which may help the long-term health of trans people around the world.”

The Swedish Society for Medical Research, the Swedish Research Council, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, and the European Research Council (ERC) all provided funding for the study.

Source Link: Imperial College London