# Lipid dysregulation of immune mediated intestinal epithelial healing

> **NIH NIH K01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $152,923

## Abstract

Lipid dysregulation of immune mediated intestinal epithelial healing
A single layer of epithelial cells protects us from harmful interactions with the intestinal microbiota and harmful
agents we inhale and ingest daily. Unresolved damage to this epithelial layer can lead to the development of
chronic inflammatory diseases, including inflammatory bowel disease (IBD). High fat diets (HFD) correspond to
increased incidence and severity of many chronic inflammatory diseases. Diets high in fat have been
demonstrated to directly induce pro-inflammatory functions in macrophages, promoting chronic inflammation. In
the intestine, HFD has been shown to decrease barrier function and promote chronic inflammation. However,
it’s impact on intestinal immune function and tissue repair processes is less understood.
 Our immune system supports the proper functioning of tissue barriers. In response to tissue damage,
tissue macrophages induce pro-inflammatory immune functions aiding in protection from pathogens. In the
resolution phase of this response, these cells produce anti-inflammatory cytokines to dampen inflammation and
promote tissue repair. Perturbations to any aspect of this response can lead to ineffective repair of tissue injury
and development of inflammation. A key signal involved in this molecular switch of macrophages from pro- to
anti-inflammatory responses is clearance of apoptotic cells, specifically apoptotic neutrophils. Defects in this
response have been linked to many auto-immune and chronic inflammatory diseases including lupus, type 1
diabetes, atherosclerosis, COPD and cardiovascular disease. Tissue macrophages are important in intestinal
homeostasis and their dysfunction is thought to drive disease pathogenesis in IBD. Further, defective barrier
repair is seen in intestinal disease, but it is unclear whether defective apoptotic cell clearance by intestinal
macrophages is involved and what mechanisms could modulate this process.
 To determine the impact of HFD on intestinal tissue repair responses, we utilized short-term HFD feeding
in the context of mouse models of intestinal injury. Our data demonstrates that HFD increases susceptibility to
colitis with increased weightloss, aberrant epithelial cell proliferation, loss of goblet cells and tight junction
proteins necessary to prevent microbial penetration into the body. Further, we identified dysregulated immune
responses resulting in an inability of intestinal immune cells to properly support barrier function and repair. We
also find that HFD alters macrophage responses to and clearance of apoptotic neutrophils. Together, we find
that HFD feeding directly promotes altered functions of intestinal immune cells leading to barrier repair defects.
These findings led us to hypothesize that dietary lipids directly interfere with apoptotic cell recognition and uptake
receptors and activation of downstream pro-repair signaling pathways resulting in dysregulated intestinal barrier
repair. This is t...

## Key facts

- **NIH application ID:** 10140334
- **Project number:** 5K01DK121934-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Andrea Alyssa McAlester
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $152,923
- **Award type:** 5
- **Project period:** 2020-04-07 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140334

## Citation

> US National Institutes of Health, RePORTER application 10140334, Lipid dysregulation of immune mediated intestinal epithelial healing (5K01DK121934-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10140334. Licensed CC0.

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