Serum amyloid A delivers retinol to intestinal myeloid cells to promote adaptive immunity

Abstract

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 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 low-density lipoprotein (LDL) receptor-related protein 1 (LRP1) as an SAA receptor that endocytoses SAA-retinol complexes and promotes retinol acquisition by RA-producing intestinal myeloid cells. Consequently, SAA and LRP1 are essential for vitamin A-dependent immunity, including B and T cell homing to the intestine and immunoglobulin A production. Our findings identify a key mechanism by which vitamin A promotes intestinal immunity.