Epithelial retinoic acid receptor β regulates serum amyloid A expression and vitamin A-dependent intestinal immunity

Proc Natl Acad Sci U S A. 2019 May 28;116(22):10911-10916. doi: 10.1073/pnas.1812069116. Epub 2019 May 16.

Abstract

Vitamin A is a dietary component that is essential for the development of intestinal immunity. Vitamin A is absorbed and converted to its bioactive derivatives retinol and retinoic acid by the intestinal epithelium, yet little is known about how epithelial cells regulate vitamin A-dependent intestinal immunity. Here we show that epithelial cell expression of the transcription factor retinoic acid receptor β (RARβ) is essential for vitamin A-dependent intestinal immunity. Epithelial RARβ activated vitamin A-dependent expression of serum amyloid A (SAA) proteins by binding directly to Saa promoters. In accordance with the known role of SAAs in regulating Th17 cell effector function, epithelial RARβ promoted IL-17 production by intestinal Th17 cells. More broadly, epithelial RARβ was required for the development of key vitamin A-dependent adaptive immune responses, including CD4+ T-cell homing to the intestine and the development of IgA-producing intestinal B cells. Our findings provide insight into how the intestinal epithelium senses dietary vitamin A status to regulate adaptive immunity, and highlight the role of epithelial cells in regulating intestinal immunity in response to diet.

Keywords: intestinal epithelium; microbiota; mucosal immunity; retinol; vitamin A.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Gastrointestinal Microbiome / physiology
  • Hep G2 Cells
  • Humans
  • Immunity, Mucosal / physiology*
  • Intestinal Mucosa / metabolism*
  • Mice
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Serum Amyloid A Protein / genetics
  • Serum Amyloid A Protein / metabolism*
  • Vitamin A / metabolism*

Substances

  • Receptors, Retinoic Acid
  • Serum Amyloid A Protein
  • retinoic acid receptor beta
  • Vitamin A