Ricerc@Sapienza

Accumulating evidence supports the notion that systemic and cellular metabolism profoundly affects the functions of immune cells. Whether lifelong hypolipidemia impacts immune cell proportions and functions is completely unknown. Familial Combined Hypolipidemia (FHBL2) is a rare genetic disorder characterised by very low levels of plasmatic lipoproteins and caused by mutations in the angiopoietin-like 3 (ANGPTL3) gene, encoding for a protein that inhibits extracellular lipases. FHBL2 condition is not associated with an increased risk of immune-mediated diseases and thus represents a unique platform to test the immunoprotective effects of hypolipidemia. Here we propose to investigate immune functions in FHBL2 subjects through an unbiased transcriptomic analysis of peripheral blood mononuclear cells. To this aim, RNA will be extracted and RNA-Seq will be performed in cells obtained from 4 FHBL2 and age- and sex-matched healthy controls, and results will be analysed in order to reveal which immune cell subsets may be represented at different frequencies, and which immune and non-immune pathways may be altered, in FHBL2 subjects compared to controls. This proposal stems from the collaboration between two groups with complementary expertise in immunology and in lipid metabolism, and is expected to generate novel information about immune-metabolic crosstalk which may have important implications for understanding and treating dyslipidemias and metabolic syndrome.