Monday, June 30, 2025 6/30/2025

Human M Cells Require Coronin 1a

Award Number: R01AI180038
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/20/2023
PERIOD OF PERFORMANCE END DATE: 10/31/2028

Group Awards By:

View Award Description

Human M Cells Require Coronin 1a - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $685,191 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	000	2	10/31/2024	NON-COMPETING CONTINUATION	$685,191
														Subtotal = $685,191

Issue Date FY: 2024 ( Subtotal = $706,382 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	000	1	11/17/2023	NEW	$635,744
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	001	1	9/5/2024	NEW	$70,638
														Subtotal = $706,382

Grand Total All Awards = $1,391,573

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Human M Cells Require Coronin 1a

Award Number: R01AI180038

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 11/20/2023

PERIOD OF PERFORMANCE END DATE: 10/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer