[Milieu Intérieur: understanding healthy immune system heterogeneity to move along the path towards personalized medicine].

The Milieu Intérieur project aims to define the boundaries of a healthy immune system in steady state and upon immune stimulation, and to elucidate environmental and hereditary determinants of its variability. The project is based on an in-depth immune phenotyping of 1 000 healthy donors. By correlating the cytometry measurements of peripheral blood immune cell composition in homeostasis, with the associated metadata, we have defined reference values of phenotypes related to sex and age, and found a significant impact of latent cytomegalovirus infection and smoking on measured phenotypes. In addition, we identified eleven novel Single-Nucleotide Polymorphisms (SNPs) associated with immune cell phenotypes. Immune response signatures were measured upon stimulation of fresh peripheral blood by 40 immune stimuli. Robust and standardized pipelines were established to quantify expression of 29 proteins and 572 genes and to explore genetic and non-genetic determinants of the variability of healthy immune response. The analytical approaches established by Milieu Intérieur and the collected data set represent an ideal reference for comparison studies of disease populations.