# Regulation of Intestinal Immunity by Aryl Hydrocarbon Receptor Signaling in Necrotizing Enterocolitis

> **NIH NIH F32** · WASHINGTON UNIVERSITY · 2021 · $75,330

## Abstract

PROJECT SUMMARY/ABSTRACT
Necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in preterm infants in the
neonatal intensive care unit (NICU). The discovery of effective therapeutic and preventative strategies against
NEC remains an ongoing priority. Although the multiple components of the innate and adaptive immune system
have a described role in the pathogenesis of NEC, the overall immune cell signature during NEC compared to
intestinal homeostasis has not been described. Preliminary data has shown the important anti-inflammatory role
of the aryl hydrocarbon receptor and its dietary ligand, indole-3-carbinol, in attenuating inflammation during NEC
and preserving intestinal architecture. The preliminary data further shows that mice lacking AhR in CD11c+ cells
(AhR∆CD11c) have an increased expression of pro-inflammatory IL-1β during NEC, whereas mice lacking AhR in
the intestinal epithelial cells (IEC) (AhR∆IEC) experience no difference in the severity of NEC. The anti-
inflammatory functions of some dietary AhR ligands have been described in adult experimental colitis, but their
role in NEC is unknown. Therefore, this proposal tests the central hypothesis that the inflammation in the small
intestine of infants with NEC contains a distinct immune cell infiltrate and that dietary AhR ligands activate
signaling pathways during NEC to attenuate the inflammatory response. This proposal will use next generation
sequencing tools to evaluate the immune cell infiltrate of the small intestine during our experimental murine
model of NEC and in surgically resected human small intestine NEC tissue. Further, the effects of a dietary AhR
ligand on the pro-inflammatory response and epithelial barrier dysfunction during NEC will be investigated using
our experimental murine NEC in wild-type mice, mice with AhR cell-specific knockouts, and human preterm
enteroids. This research has significant translational relevance and addresses a critical knowledge gap in the
understanding of the immune-related mechanisms in NEC pathogenesis. The outcomes of this work will define
how a dietary ligand supplement to infants with immature immunity and immure gut barrier function may serve
as a novel immunotherapeutic and nutritional strategy to protect the intestine against this deadly disease.

## Key facts

- **NIH application ID:** 10311910
- **Project number:** 1F32DK130248-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Lila Sarah Sanning
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,330
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10311910

## Citation

> US National Institutes of Health, RePORTER application 10311910, Regulation of Intestinal Immunity by Aryl Hydrocarbon Receptor Signaling in Necrotizing Enterocolitis (1F32DK130248-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10311910. Licensed CC0.

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