Wednesday, July 2, 2025 7/2/2025

Mechanisms of immune-epithelial crosstalk in tissue repair

Award Number: R01AI168462
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: 02/07/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

Mechanisms of immune-epithelial crosstalk in tissue repair - PROJECT SUMMARY The skin serves as a primary barrier to the external world and is thus often injured. As such, rapid repair of tissue damage is vital for organismal survival. Failure to repair wounds results in the formation of chronic or non-healing wounds, which affect over 2% of the western population and cost an estimated 25 billion dollars to manage annually. Immunosuppression is one major predisposing factor to chronic wound formation, indicating that signals derived from immune cells are necessary for optimal repair. Yet, there is a significant gap in our understanding of exactly how immune cells are activated and precisely how they crosstalk with the epithelium to direct repair. Normal skin comprises a myriad of “homeostatic” immune cell types that actively patrol the tissue in health and we find are rapidly activated and recruited to the site of injury. These include type 17 immune cell subsets that have only been uncovered in the last 10 years and whole function in repair has not been studied in immunocompetent animals. We systematically ablated each type 17 cell type to determine their role in activating the wound edge epithelium and found that in type17-γδ T cells, but not other subsets are absolutely necessary for wound -re-epithelialization. This crosstalk is mediated by the prototypic cytokines IL-17A/F signaling directly into the epithelium via their receptor IL-17RC. Surprisingly, we uncovered that IL17RC signaling activates HIF1a protein, and that this signaling axis is required for optimal HIF1a activation at the wound edge even in the pres- ence of hypoxia. Loss of epithelial HIF1a profoundly disrupts wound re-epithelization indicating that this tran- scription factor is a master regulator of epithelial activation at the wounds edge. While type17-γδ T cells have been studied in pathogen responses, how they are recruited and activated in wounds is poorly understood. Additionally, exactly how IL17 signaling induces HIF1a is unclear and the molecular targets of HIF1a that drive repair require elucidation. We will address these fundamental questions in two independent aims: (1) How are type17-γδ T cells recruited to and activated at the wound’s re-epithelizing front? ; (2) How does inflammatory HIF1a control re- epithelialization programs downstream of IL-17? Decoding the molecular interactions between wound-associ- ated lymphocytes and would edge epithelium, as we propose here, is an essential first step in finding immune- based therapies for chronic non-healing wounds. Moreover, many inflammatory conditions and cancers, driven by type 17 immunity, co-opt features wound repair. Thus, our studies will not only unearth fundamental mecha- nisms of immune-epithelial crosstalk in repair, but may also provide novel therapeutic targets for a range of type17 immunity-mediated epithelial pathologies.


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 = $608,645 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	000	5	12/20/2024	NON-COMPETING CONTINUATION	$608,645
2025	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	001	3	2/18/2025	NON-COMPETING CONTINUATION	-$157,909
2025	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	002	4	2/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$157,909
														Subtotal = $608,645

Issue Date FY: 2024 ( Subtotal = $629,326 )
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	002	3	8/28/2024	NON-COMPETING CONTINUATION	-$92,005
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Allergy and Infectious Diseases Research	003	4	8/28/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$92,005
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	3	1/9/2024	NON-COMPETING CONTINUATION	$566,394
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	001	3	5/23/2024	NON-COMPETING CONTINUATION	$62,932
														Subtotal = $629,326

Issue Date FY: 2023 ( Subtotal = $603,073 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	1/5/2023	NON-COMPETING CONTINUATION	$603,073
														Subtotal = $603,073

Issue Date FY: 2022 ( Subtotal = $586,123 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	2/7/2022	NEW	$586,123
														Subtotal = $586,123

Grand Total All Awards = $2,427,167

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of immune-epithelial crosstalk in tissue repair

Award Number: R01AI168462

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: 02/07/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer