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

Sureka Gattu, Ye Ji Bang, Mihir Pendse, Chaitanya Dende, Andrew L. Chara, Tamia Harris-Tryon, Yuhao Wang, Kelly A. Ruhn, Zheng Kuang, Shanthini Sockanathan, Lora V Hooper

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)10911-10916
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume166
Issue number22
DOIs
Publication statusPublished - May 28 2019

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Keywords

  • Intestinal epithelium
  • Microbiota
  • Mucosal immunity
  • Retinol
  • Vitamin A

ASJC Scopus subject areas

  • General

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