bioRxiv Science⌕ Search

Biology subjects

Propheter, D. C.

Publications and source records attributed to Propheter, D. C..

2 recordsLinked to original sources
bioRxiv2026

Epithelial sensing of vitamin A shapes intestinal antimicrobial defense

Vitamin A is a central regulator of intestinal adaptive immunity, but its role in innate immunity is less defined. Antimicrobial proteins form a chemical barrier that protects the intestinal epithelium from microbial invasion. Among these, REG3 family lectins are induced by the microbiota, yet how nutritional cues intersect with microbial signals to control their expression remains 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. This induction is mediated by retinoic acid and requires retinoic acid receptor (RAR) signaling. Mechanistically, RARs bind directly to the Reg3g promoter adjacent to a STAT3 binding site. As STAT3 mediates microbiota-induced IL-22 signaling in epithelial cells, this arrangement provides a molecular framework for 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 -defensin antimicrobial proteins. Together, these findings define a transcriptional mechanism by which vitamin A enhances epithelial antimicrobial defenses and strengthens mucosal innate immunity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/710399v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@18dd8aforg.highwire.dtl.DTLVardef@18cf2fdorg.highwire.dtl.DTLVardef@a4dc89org.highwire.dtl.DTLVardef@18aa9c7_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIVitamin A promotes epithelial expression of REG3 antimicrobial proteins in the intestine C_LIO_LIRetinoic acid receptors (RARs) directly activate mouse Reg3g and human REG3G transcription C_LIO_LIRARs bind the Reg3g promoter adjacent to STAT3, integrating nutritional and microbial signals C_LIO_LIVitamin A-RAR signaling broadly regulates epithelial antimicrobial programs, including -defensins C_LI

immunology↗
bioRxiv2022

Macrophages regulate gastrointestinal motility through complement component 1q

Peristaltic movement of the intestine propels food down the length of the gastrointestinal tract to promote nutrient absorption. Interactions between intestinal macrophages and the enteric nervous system regulate gastrointestinal motility, yet we have an incomplete understanding of the molecular mediators of this crosstalk. Here we identify complement component 1q (C1q) as a macrophage product that regulates gut motility. Macrophages were the predominant source of C1q in the mouse intestine and most extraintestinal tissues. Although C1q mediates complement-mediated killing of bacteria in the bloodstream, we found that C1q was not essential for immune defense of the intestine. Instead, C1q-expressing macrophages were localized to the intestinal submucosal plexus where they closely associated with enteric neurons and expressed surface markers characteristic of nerve-adjacent macrophages in other tissues. Mice with a macrophage-specific deletion of C1qa showed changes in enteric neuronal gene expression, increased peristaltic activity, and accelerated intestinal transit. Our findings identify C1q as a key regulator of gastrointestinal motility and provide enhanced insight into the crosstalk between macrophages and the enteric nervous system.

immunology↗