Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 22, Pages 10911-10916Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1812069116
Keywords
vitamin A; retinol; microbiota; intestinal epithelium; mucosal immunity
Categories
Funding
- NIH [R01 DK070855, T32 AI007520]
- Welch Foundation [I-1762]
- Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases
- Howard Hughes Medical Institute
- Burroughs Wellcome Foundation
- Dermatology Foundation
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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 beta (RA beta) is essential for vitamin A-dependent intestinal immunity. Epithelial RAR beta 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 RAR beta promoted IL-17 production by intestinal Th17 cells. More broadly, epithelial RAR beta 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.
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