GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE

The Milieu Intérieur (MI) project was established in 2011 with the aim to define the parameters that characterise a healthy immune response and its natural variation across individuals and, in doing so, inform clinical strategies for managing disease. MI recruited a 1,000 healthy donor cohort, stratified by age and sex, from whom we built a biocollection consisting of genomic DNA, fecal samples, nasal swabs, stimulated whole blood supernatants and cell pellets, as well as fibroblast cell lines and iPSCs. These biological materials form the basis for a rich and growing data warehouse hosted at Institut Pasteur. Through the integrative analyses of multiple datasets, we quantified the extent of genetic control of cellular variability, transcriptional and humoral responses to infection, thymic function, as well as immune variability determined by the host microbiota. Ongoing work on the environmental and social factors that impact immunity is being carried out. Collaborations with CNRGH-CEA, Institut Roche, Genentech and Sanofi have also led to a unique, rich dataset of complete host and microbiome genomes, enabling to evaluate their impact on immune responses. MI recently completed a longitudinal 10-year follow-up study on the cohort. From this new study we are analysing how aging, genetics and environmental exposures affect immune variability and to assess health impacts occurring in this well-defined population. A recent partnership with Scienta Lab will apply novel artificial intelligence algorithms to provide new insights into the factors shaping immune variability. Through extensive collaborative partnerships, we have extended our approach to other healthy populations in Senegal and Hong Kong, as well as other age groups (neonatal, paediatric, and geriatric). The “MI concept” has been applied to 27 clinical studies, through which previously unknown immune perturbations have been identified in diverse conditions, ranging from infection to autoimmunity and cancer.