Microbiota-induced vitamin A mobilization by serum amyloid A and its role in intestinal immunity

Vitamin A and its derivative retinol are essential for the development of intestinal adaptive immunity. Retinoic acid (RA)-producing myeloid cells are central to this process, but how myeloid cells acquire retinol for enzymatic conversion to RA is unknown. Here, we show that serum amyloid A (SAA) proteins, retinol binding proteins induced in intestinal epithelial cells by the microbiota, deliver retinol to myeloid cells. We identify LDL receptor-related protein 1 (LRP1) as an SAA receptor that facilitates endocytosis of SAA-retinol complexes and promotes retinol acquisition by RA-producing intestinal myeloid cells. Consequently, SAA and LRP1 are essential for the development of vitamin A-dependent adaptive immunity, including B and T cell homing to the intestine and IgA production, and promote protection against enteric infection after immunization. Our findings identify a key mechanism underpinning vitamin A’s effects on the immune system and provide insight into how the microbiota promotes intestinal immunity.