SLC7A7/Y+LAT1, mutated in Lysinuric protein intolerance, has a significant role in regulating the inflammatory status of human macrophages

Abstract

Lysinuric protein intolerance (LPI) is a recessively inherited aminoaciduria caused by mutations of SLC7A7, the gene that encodes y+LAT1 light chain of system y+L for cationic amino acids (CAA; namely arginine, lysine, and ornithine) transport. Clinical signs of LPI are highly heterogeneous and only poorly understood: while hyperammonemia and protein intolerance can be explained by urea cycle slowdown due to the impairment of CAA absorption/reabsorption in intestinal and renal epithelial cells, little is known about the pathogenesis of the often fatal complications affecting lungs and immune system. Here, we explore the possibility that y+LAT1 protein directly exerts immunomodulatory functions and that LPI defects, besides affecting CAA transport, also activate inflammatory mononuclear phagocytes, ultimately leading to immunological complications.