# Human M Cells Require Coronin 1a

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $706,382

## Abstract

Project Summary/Abstract
 The regulation of luminal surveillance and antigen sampling across mucosal surfaces remains an important
and fundamental area of investigation. This is particularly true for the intestinal epithelium, which is constantly
challenged to maintain homoeostasis with the complex microbiome while protecting the mucosa from pathogenic
organisms. Microfold (M) cells of the Peyer’s patch (PP) play a crucial role in immune surveillance of the gut
environment by transporting luminal antigens to underlying immune cells. Through their ability to move cargo
across the epithelium, M cells can (1) benefit the host by translocating luminal contents (e.g. dietary antigens,
microbes, vaccines) to induce appropriate innate and adaptive immune responses or (2) harm the host upon
infection by invasive pathogens. However, the mechanisms responsible for antigen uptake by M cells and
delivery to immune cells are not completely understood in humans. The significance of our proposed research
is that we will define the basic mechanism responsible for the major function (i.e. transcytosis) of human M cells.
Revealing what controls transcytosis in human M cells has the potential to improve our understanding of how
luminal gut contents are delivered to immune cells under normal conditions or during enteric infections. Our
recent discoveries using human enteroids enriched in M cells as a relevant ex vivo model of the human PP
epithelium demonstrate that (1) coronin 1a is required for uptake and transcytosis of luminal cargo across human
M cells, (2) update and transcytosis of gut antigens occurs by a apical-dependent bulk endocytosis process that
involves coronin 1a-mediated signaling, and (3) PP macrophages synergize with M cell-expressing human
enteroids to increase M cell-dependent uptake and transcytosis of luminal gut. SPECIFIC AIMS: We propose
to test the hypotheses that human M cell expressing enteroids respond to luminal microbial and serosal
immune signals to induce uptake and transcytosis of gut cargo by a unique coronin 1a dependent
mechanism. Our central hypotheses are that coronin 1a expression in human M cells is necessary for: (i)
terminal differentiation of FAE progenitor cells to become functionally mature M cells, (ii) synergism between PP
macrophages and the human FAE to enhance luminal sampling of gut antigens, and (iii) mediating luminal- and
serosal-derived signals that stimulate entry and transcytosis of luminal gut cargo to underlying immune cells.
The studies will improve our understanding of how human M cells function and may lead to development of novel
therapeutic strategies to treat GI disorders, such as Crohn’s disease, or even possibly development of new
strategies to enhance oral vaccine delivery.

## Key facts

- **NIH application ID:** 10779680
- **Project number:** 1R01AI180038-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Nicholas Constantine Zachos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $706,382
- **Award type:** 1
- **Project period:** 2023-11-20 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10779680

## Citation

> US National Institutes of Health, RePORTER application 10779680, Human M Cells Require Coronin 1a (1R01AI180038-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10779680. Licensed CC0.

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