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

Science. 2021 Sep 17;373(6561):eabf9232. doi: 10.1126/science.abf9232. Epub 2021 Sep 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • B-Lymphocytes / immunology
  • CD11c Antigen / analysis
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Line
  • Endocytosis
  • Gene Deletion
  • Humans
  • Immunoglobulin A / biosynthesis
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestine, Small / cytology
  • Intestine, Small / immunology*
  • Intestine, Small / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism*
  • Protein Binding
  • Retinol-Binding Proteins / metabolism
  • Salmonella Infections, Animal / immunology
  • Salmonella typhimurium
  • Serum Amyloid A Protein / genetics
  • Serum Amyloid A Protein / metabolism*
  • Th17 Cells / immunology
  • Vitamin A / metabolism*

Substances

  • CD11c Antigen
  • Immunoglobulin A
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Lrp1 protein, mouse
  • Retinol-Binding Proteins
  • Saa2 protein, mouse
  • Serum Amyloid A Protein
  • Vitamin A