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Characterizing circulating and visceral T cells specific for the autoantigen integrin αvβ6 in ulcerative colitis

Award Number: R21AI188483
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: 12/04/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Characterizing circulating and visceral T cells specific for the autoantigen integrin αvβ6 in ulcerative colitis - PROJECT SUMMARY/ABSTRACT The integrin heterodimer αvβ6 expressed on intestinal epithelial cells has recently been discovered as the target of autoantibodies uniquely found in nearly every patient with ulcerative colitis (UC), even years before disease onset. We propose to find and characterize the T cells ultimately responsible for letting B cells make these antibodies, and thus reveal a novel insight into how immune self-tolerance to a mucosal autoantigen is lost in UC, or conversely maintained in people without UC. To this end, we will adapt the Activation Induced Marker (AIM) assay that we have used extensively in the study of type 1 diabetes to now evaluate UC. This will allow us for the first time to employ this assay on cells from the mesenteric lymph nodes of humans, where much of the T cell-B cell interactions necessary for gut-centric antibody production occur, and leverage data thus generated into an analysis of the colonic mucosa itself. We are able to do this because we uniquely have a bank of cryopreserved live MLN and colon samples from the surgical resections of dozens of people with UC and Crohn's disease, in addition to cryopreserved live blood cells and serum from hundreds of other UC patients and healthy controls. The AIM assay is designed to independently evaluate pro-inflammatory and regulatory T cells. In addition to finding and immunophenotyping autoantigen-specific T cells by flow cytometry, the AIM assay will allow us to isolate these cells for single-cell analyses of their gene expression profiles and unique T cell receptor sequences. These in turn serve as a unique identifier with which to track autoantigen- specific T cells throughout the body, including in the colon, where autoreactive T cells may play a direct role in promoting or suppressing pathology.


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: 2026 ( Subtotal = $216,625 )
2026	2026	BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON	1201 9TH AVE	SEATTLE	WA	98101	KING	USA	Allergy and Infectious Diseases Research	000	2	12/24/2025	NON-COMPETING CONTINUATION	$216,625
														Subtotal = $216,625

Issue Date FY: 2025 ( Subtotal = $252,152 )
2025	2025	BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON	1201 9TH AVE	SEATTLE	WA	98101	KING	USA	Allergy and Infectious Diseases Research	000	1	12/4/2024	NEW	$252,152
														Subtotal = $252,152

Grand Total All Awards = $468,777

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Characterizing circulating and visceral T cells specific for the autoantigen integrin αvβ6 in ulcerative colitis

Award Number: R21AI188483

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: 12/04/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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