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 language | English (US) |
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Pages (from-to) | 10911-10916 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 166 |
Issue number | 22 |
DOIs | |
State | Published - May 28 2019 |
Keywords
- Intestinal epithelium
- Microbiota
- Mucosal immunity
- Retinol
- Vitamin A
ASJC Scopus subject areas
- General