Approved Research

Evaluating sex differences in inflammation and immune system function

Lay summary

There are large differences in immune system function between men and women: rates and severity of infectious, autoimmune, and inflammatory diseases, vaccine response, and immune aging all differ substantially. Sex is the largest risk factor for many of these human traits and understanding such sex differences could change the way we think about them, allowing us to provide better and more targeted treatment, or driving the development of new public health policies.

We know very little about the causes of these differences, but it is likely that they are both genetic and environmental. We already know that overall, many of these traits have a large genetic component, so we suspect that some of these genetic factors also define the sex differences we see. Many of these traits have been measured in the UK Biobank participants, so we are requesting access to these data to test our ideas.

We also know that inflammation - a key function of the immune system - is important in a wide variety of diseases that are not usually thought of as "immune", though many also differ between men and women (heart disease, for example). We would like to test if differences between the sexes, and variability within each sex, can explain the differences we see in these other diseases. We therefore request access to data relevant to those diseases.

Sex hormones are an obvious explanation for sex differences, as they vary between the sexes and have diverse biological functions. In our laboratory, we have found that oestrogen, a sex hormone far more abundant in women than men, changes how immune cells behave. If these hormones explain differences between sexes, they should also explain some differences within each sex. Not all women develop immune disease, and some men do; if sex hormones affect this risk, then we would expect hormone levels within women to predict who develops disease. Similarly, we expect those levels to predict disease in men. We therefore request access to sex hormone levels, which have also been measured in UKBB participants.

Overall, we aim to assess differences between men and women, and expect to test a wide range of hypotheses. Long term, we expect this work to inform how we treat men and women with a wide variety of diseases, and whether different treatments might be optimal. As we expect to generate hypotheses from our analyses, we request a rolling three-year period of access.