“The immune system varies remarkably between individuals and is regulated by a multitude of factors such as genetics, persisting infections, age and environment. Immune homeostasis is tightly controlled, and immune perturbations caused by human diseases revert to baseline upon disease resolution. It remains largely unknown how inter-individual immune variation contributes to the susceptibility of diseases including autoimmunity and infections. However, such knowledge is important to better understand disease mechanisms and for the discovery of new therapeutic targets.
Here, we combine high-dimensional flow cytometry from 2300 healthy individuals with genetic, metabolomic, microbiome and systems serology data to study the mechanisms of immune homeostasis at population scale. Such large immunophenotyping studies require thorough and precise sample processing and data analysis methods to ensure low inter-experimental variation and optimal precision for sensitive measurements. We will present our high-throughput flow cytometry pipeline, which enabled us to process 200 samples per experiment, and discuss strategies to assess and eliminate several sources of technical and experimental errors.
Our data enabled us to investigate the influence of genetics, age and sex on immune variation. Sex-dependent differences in the immune system impact the risk of diseases as exemplified by the higher prevalence of autoimmune diseases in females. We discovered multiple sex-dependent immune traits, which may help to better understand the impact of sex-dependent immune differences on disease susceptibility. Similarly, ageing is associated with changes in immune functions. Consequently, immune ageing leaves elderly more prone to diseases such as infections and cancer. Our analysis confirmed previously known and revealed more refined age-associated immune dynamics. Thus, we provide new insights into the mechanisms of immune ageing. Lastly, we will provide some insights into our genome-wide association studies, which revealed immune traits that are almost entirely regulated by genetics. Thus, our data will provide new insights into the interplay between genetics and the immune system. Overall, our large immunophenotyping study provides comprehensive insights into the various facets of immune homeostasis and its role in human health at the population scale.”
