Dataset Information

Epithelial sensing of vitamin A shapes intestinal antimicrobial defense

ABSTRACT: Antimicrobial proteins form an essential chemical barrier that protects the intestinal epithelium from microbial invasion. REG3 family antimicrobial lectins are prominently induced by the microbiota, but how nutritional cues intersect with microbial signals to regulate their expression is poorly understood. Vitamin A plays a central role in mucosal adaptive immunity, but its contribution to epithelial innate immunity is unclear. Here, we show that dietary vitamin A promotes expression of REG3 antimicrobial lectins, including REG3G, in intestinal epithelial cells from both mice and humans. Vitamin A–dependent induction of REG3G expression is driven by retinoic acid and requires signaling through retinoic acid receptors (RARs). Mechanistically, RARs directly bind the Reg3g promoter adjacent to a binding site for STAT3, the transcription factor that transduces microbial signals, thereby integrating nutritional and microbial inputs at the level of REG3G transcription. Extending these findings, we demonstrate that vitamin A–retinoic acid signaling similarly promotes expression of α-defensin antimicrobial proteins. Together, these results define a transcriptional mechanism by which vitamin A enhances epithelial antimicrobial defenses to strengthen mucosal innate immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE318054 | GEO | 2026/03/08

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Objective: Reg3g has been proposed to have a protective role against infection due to its bactericidal effect on Gram-positive bacteria, but evidence from in vivo studies is lacking. Therefore we generated a Reg3g-/- mouse, to determine its role in intestinal homeostasis and protection against experimental infection. Methods: Reg3g-/- mice were phenotyped using histological methods and a range of innate and immune markers. To investigate the antimicrobial role of Reg3g we experimentally infected mice with Gram-positive Listeria monocytogenes and Gram-negative Salmonella entertitidis and measured translocated bacteria, mucosal and systemic markers of infection. Results: Reg3g-/- mice display altered ileal mucus distribution and increased bacterial contact with the epithelium. , concomitant with This increased the inflammatory status in of the ileal mucosa and increased expression of Il-22, myeloperoxidase (MPO) and serum chemokines in serum. In response to infection, Reg3g-/- mice showed transcriptome changes and elevated levels of mucosal MPO in the ileum, but no increased bacterial translocation to the organs. Conclusions: Reg3g is equally distributed throughout the mucus of wild type (wt) mice and its absence results in an altered distribution of the ileal mucus. Reg3g deficiency also results resulted in increased bacterial contact with the epithelium and heightened inflammatory responses in the ileal mucosa. We propose that Reg3g binds pathogens suggesting it and contributes to mucus barrier function by ensnaring bacteria. Compared to wt mice, Reg3g-/- mice infected with S. enteritidis and L. monocytogenes show an increase of mucosal inflammatory markers indicating the protective, anti-microbial roles of Reg3g in defence against both Gram-positive and -negative bacteria. This study was set up according to a one-treatment, one-control design; treatments were inoculation with either Listeria monocytogenes or Salmonella enteritidis bacterial pathogens. The study results contain transcriptional profiles from infected and sham-infected control C57Bl/6 mice. In total, this study includes data from 2 treatments and 1 control of (pooled) wild-type C57Bl/6 mice and Reg3g-/- KO mutant C57Bl/6 mice = 6 arrays.

Dataset Information

Epithelial sensing of vitamin A shapes intestinal antimicrobial defense

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets