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Mechanisms and consequences of T cell inflammasome activation in Graft-Versus Host Disease

Award Number: R21AI171879
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: 08/15/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Mechanisms and consequences of T cell inflammasome activation in Graft-Versus Host Disease - Graft Versus Host Disease (GVHD) remains a significant issue in people receiving hematopoietic cell transplants to treat various cancers, genetic immunodeficiencies and other diseases. In GVHD, alloreactive T cells mediate this pathology, as T cell depleted hematopoietic transplants to not induce GVHD. We have observed that following transplantation, donor CD8 T cells undergo inflammasome activation, as measured by the activation of caspase‐1. However, these cells do not die via pyroptosis, which may alleviate their cytotoxic consequences in the host. We also observe that these cells in which the inflammasome is activated hyperexpress a protein, Ifi202, which is known to attenuate inflammasome activation, and human T cells similarly express IFI16, which functions similarly in human cells. We hypothesize that Ifi202 limits the degree of caspase‐1 activation in these cells, and thus prevents these cells from undergoing pyroptosis. The goal of this project is to determine the mechanism of inflammasome activation in these T cells, and to determine the role of Ifi202 in preventing pyroptosis in CD8 T cells during GVHD. We hypothesize that reduced Ifi202 expression in these cells will attenuate GVHD pathology by increasing pyroptosis in alloreactive CD8 T cells.


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 = $0 )
2026	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	2	2/12/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $231,000 )
2023	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	2	7/27/2023	NON-COMPETING CONTINUATION	$231,000
														Subtotal = $231,000

Issue Date FY: 2022 ( Subtotal = $192,500 )
2022	2022	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	1	8/15/2022	NEW	$192,500
														Subtotal = $192,500

Grand Total All Awards = $423,500

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Mechanisms and consequences of T cell inflammasome activation in Graft-Versus Host Disease

Award Number: R21AI171879

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: 08/15/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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