Edoardo Fiorillo – Francesco Cucca

The main aim of the Immunogenetics lab is to highlight immune cell features that are significantly involved both into predisposition to autoimmunity and immunosenescence. The research approach combines high-resolution genetic and immune system characterization and consists of a fine dissection of the immunes system in at least 4,000 deeply genotyped individuals of the ProgeNIA community cohort (26M SNPs and 2M In/Del polymorphisms). The circulating immune system is broken down into about 340 actual counted cell populations. These populations belong to the innate and adaptive immunity cell types and about 2,000 surface marker fluorescence intensities are also monitored. Data are then analysed through GWAS and the genetic variants affecting immune traits are systematically searched in autoimmunity databases for coincident associations with autoimmune diseases in our own case-control sample set of ~3500 multiple sclerosis patients, ~2000 type 1 diabetes patients and ~3500 controls as well as in publicly available autoimmunity databases. Alterations of the circulating immune system have also been assessed for the main environmental exposures such as latent viral infections, physical activity, diet and cigarette smoking to see the extent to which they influence (or resemble) immunosenescence and to quantify how their impact varies on genetic bases. We also test the expression signature of PBMCs using the data we have from more than 600 individuals with a diverse range of ages whose RNA has been fully sequenced. Based on the preliminary data on cellular and soluble traits, our genetic and functional work plan is restricted to those variants that are the most involved in autoimmunity and ageing; to this end, selected individuals with specific genotypes in the cohort are recalled for cell specific functional experiments including whole RNAseq.