Tuesday, May 13, 2025 5/13/2025

Microbial Regulation of Retinol Transport and its Role in Intestinal Immunity

Award Number: R01DK070855
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Description

Microbial Regulation of Retinol Transport and its Role in Intestinal Immunity - Project Summary The intestinal epithelium regulates the development of adaptive immunity to gut microorganisms, yet little is known about the underlying mechanisms. Filling this knowledge gap is crucial, as many human intestinal diseases arise from dysregulated intestinal immunity. Dietary vitamin A absorbed by the intestinal epithelium is essential for key intestinal adaptive immune responses, including the homing of T and B cells to the intestine and immunoglobulin A production. These vitamin A-dependent immune responses depend on specialized intestinal myeloid cells that enzymatically convert the vitamin A derivative retinol to retinoic acid (RA). In the previous project period we unraveled a molecular mechanism by which intestinal myeloid cells acquire retinol. We discovered that serum amyloid A (SAA) proteins – microbiota-inducible epithelial cell proteins – are retinol chaperones that deliver retinol to myeloid cells via the endocytic receptor LRP1 (low density lipoprotein-related receptor 1). We found that this mechanism is essential for the development of intestinal adaptive immunity and for immune protection against pathogenic bacterial infection. This R01 renewal application will build on these findings to further define the biochemical, cell biological, and microbiological mechanisms that regulate retinol delivery to intestinal myeloid cells and thus promote vitamin A-dependent immunity. In Aim 1, we will determine how SAA-retinol complexes are assembled and secreted from intestinal epithelial cells. In Aim 2, we will identify the SAA-LRP1 interface and determine its importance for myeloid cell retinol uptake and vitamin A-dependent immunity. In Aim 3, we will define the role of the intestinal microbiota in regulating myeloid cell retinol acquisition and vitamin A-dependent immunity. These studies will provide mechanistic insight into how vitamin A is mobilized to intestinal immune cells and advance our understanding of how the gut microbiota regulates the intestinal adaptive immune system. Our findings will help identify new strategies for inhibiting or enhancing vitamin A mobilization to the intestinal immune system in order to treat infection and inflammation.


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: 2024 ( Subtotal = $424,335 )
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	20	6/19/2024	NON-COMPETING CONTINUATION	$424,335
2024	2023	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	19	6/17/2024	COMPETING CONTINUATION	$370,556
2024	2022	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	18	6/17/2024	NON-COMPETING CONTINUATION	-$364,500
2024	2021	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	6/17/2024	NON-COMPETING CONTINUATION	-$6,056
														Subtotal = $424,335

Issue Date FY: 2023 ( Subtotal = $442,014 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	19	8/23/2023	COMPETING CONTINUATION	$442,014
2023	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	8/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $442,014

Issue Date FY: 2022 ( Subtotal = $364,500 )
2022	2022	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	5/20/2022	NON-COMPETING CONTINUATION	$364,500
														Subtotal = $364,500

Issue Date FY: 2021 ( Subtotal = $364,500 )
2021	2021	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	5/11/2021	NON-COMPETING CONTINUATION	$364,500
														Subtotal = $364,500

Issue Date FY: 2020 ( Subtotal = $364,500 )
2020	2020	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	16	5/7/2020	NON-COMPETING CONTINUATION	$364,500
2020	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	15	2/4/2020	COMPETING CONTINUATION	$182,079
2020	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	2/4/2020	NON-COMPETING CONTINUATION	-$182,079
														Subtotal = $364,500

Issue Date FY: 2019 ( Subtotal = $364,500 )
2019	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	5/10/2019	COMPETING CONTINUATION	$364,500
2019	2019	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	15	5/15/2019	COMPETING CONTINUATION	$0
														Subtotal = $364,500

Issue Date FY: 2018 ( Subtotal = $345,825 )
2018	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	4/24/2018	NON-COMPETING CONTINUATION	$345,825
														Subtotal = $345,825

Issue Date FY: 2017 ( Subtotal = $345,776 )
2017	2017	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	13	6/13/2017	NON-COMPETING CONTINUATION	$345,825
2017	2013	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	5/11/2017	NON-COMPETING CONTINUATION	-$49
														Subtotal = $345,776

Issue Date FY: 2016 ( Subtotal = $345,825 )
2016	2016	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	4/18/2016	NON-COMPETING CONTINUATION	$345,825
														Subtotal = $345,825

Issue Date FY: 2015 ( Subtotal = $345,825 )
2015	2015	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	4/17/2015	NON-COMPETING CONTINUATION	$345,825
														Subtotal = $345,825

Issue Date FY: 2014 ( Subtotal = $345,825 )
2014	2014	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	3/20/2014	COMPETING CONTINUATION	$345,825
														Subtotal = $345,825

Issue Date FY: 2013 ( Subtotal = $315,194 )
2013	2013	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	5/27/2013	NON-COMPETING CONTINUATION	$315,194
														Subtotal = $315,194

Issue Date FY: 2012 ( Subtotal = $326,369 )
2012	2012	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	5/18/2012	NON-COMPETING CONTINUATION	$326,369
														Subtotal = $326,369

Issue Date FY: 2011 ( Subtotal = $414,359 )
2011	2011	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	6/15/2011	NON-COMPETING CONTINUATION	$325,599
2011	2011	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	8/10/2011	SUPPLEMENT FOR EXPANSION	$88,760
														Subtotal = $414,359

Issue Date FY: 2010 ( Subtotal = $396,250 )
2010	2010	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	4/22/2010	COMPETING CONTINUATION	$3,750
2010	2010	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	4/6/2010	COMPETING CONTINUATION	$392,500
														Subtotal = $396,250

Issue Date FY: 2009 ( Subtotal = $287,017 )
2009	2009	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	5/15/2009	NON-COMPETING CONTINUATION	$287,017
														Subtotal = $287,017

Issue Date FY: 2008 ( Subtotal = $287,017 )
2008	2008	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Digestive Diseases and Nutrition Research	000	4	5/13/2008	NON-COMPETING CONTINUATION	$287,017
														Subtotal = $287,017

Issue Date FY: 2007 ( Subtotal = $292,874 )
2007	2007	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Digestive Diseases and Nutrition Research	000	3	5/1/2007	NON-COMPETING CONTINUATION	$292,874
														Subtotal = $292,874

Issue Date FY: 2006 ( Subtotal = $301,621 )
2006	2006	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Digestive Diseases and Nutrition Research	000	2	6/2/2006	NON-COMPETING CONTINUATION	$301,621
														Subtotal = $301,621

Issue Date FY: 2005 ( Subtotal = $308,880 )
2005	2005	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75235	DALLAS	USA	Digestive Diseases and Nutrition Research	000	1	5/30/2005	NEW	$308,880
														Subtotal = $308,880

Grand Total All Awards = $6,983,006

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Microbial Regulation of Retinol Transport and its Role in Intestinal Immunity

Award Number: R01DK070855

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer