# GOBLET CELLS IN INTESTINAL IMMUNE HOMEOSTASIS

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $402,917

## Abstract

Project Summary/Abstract
The body’s largest collection of immune cells underlies the single layer epithelium lining the GI tract and
monitors the luminal contents to maintain tolerance to dietary antigens in the steady-state and to induce
immunity to pathogens during infection. How the immune system’s exposure to luminal antigens is controlled
in the steady-state to promote tolerance and during infection to avoid inappropriate responses and promote
immunity remains a significant gap in our understanding. We propose that luminal antigen delivery to the
immune system is tightly controlled, has regional variation through the GI tract, and serves to supply antigens
to the immune system and guide the phenotype of immune responses. Goblet cells (GCs) can take up luminal
substances deliver them to antigen presenting cells in the underlying lamina propria (LP) in a manner capable
of inducing adaptive immune responses, in a process termed Goblet cell-associated Antigen Passages
(GAPs). GAP formation is induced by acetylcholine acting on GCs, is linked with secretion, and is inhibited by
GC intrinsic sensing of the gut microbiota. We propose that the pathways controlling GAP formation and the
properties of GAPs in various regions of the GI tract allow for a regional antigen delivery supporting tolerance
to dietary antigens in the steady-state and limiting immune responses to innocuous luminal antigens and
shifting the phenotype of the immune response during enteric infection. These observations give rise to the
overarching hypothesis that GC-mediated antigen delivery occurs via bulk endocytosis (BE) in GCs, is a major
and closely regulated mechanism promoting tolerance in the steady-state, and inhibition of this pathway shifts
immune responses to promote pathogen clearance and immunity during infection. To explore this hypothesis
we propose the following specific aims: Aim 1 will define the ultrastructural basis and cellular biology of GAP
formation using state-of-the-art imaging approaches, and genetic and pharmacologic manipulation of
endocytosis and GAPs. Aim 2 will define the role of GC/GAPs in the induction and maintenance of tolerance to
luminal antigens in the steady-state using genetic manipulation of GAP formation. Aim 3 will define if altering
GCs/GAPs results in inappropriate inflammatory responses to dietary antigens and/or worsened outcomes
during infection using genetic manipulation of GAPs in Salmonella typhimurium infection.

## Key facts

- **NIH application ID:** 9964770
- **Project number:** 5R01DK097317-09
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Rodney D Newberry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,917
- **Award type:** 5
- **Project period:** 2012-09-17 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964770

## Citation

> US National Institutes of Health, RePORTER application 9964770, GOBLET CELLS IN INTESTINAL IMMUNE HOMEOSTASIS (5R01DK097317-09). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9964770. Licensed CC0.

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