Sunday, March 15, 2026 3/15/2026

γδTCR-dependent and independent differentiation of innate lymphoid cells

Award Number: R01AI178947
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: 07/20/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2025
AWARD TERMINATION DATE: 04/18/2025

Group Awards By:

View Award Description

γδTCR-dependent and independent differentiation of innate lymphoid cells - ABSTRACT Innate lymphoid cells (ILCs) reside in tissues and act as sentinels to a variety of environmental cues from nutrients, neuropeptides, microbiota to pathogens. They are heterogeneous populations with diverse functions and developmental origins. We have previously suggested that in addition to the bone marrow, the thymus can contribute to ILC pools in peripheral tissues based on findings that lung ILC2s contain rearranged T cell receptor genes, likely due to the divergence of developing thymocytes into the ILC fate. Consistently, T cell precursors from the thymus can differentiate into ILC2s in vitro. Single cell RNA sequencing studies detected a heterogeneous population of ILC precursors in the blood, which is greatly diminished in athymic nude mice, suggesting the involvement of the thymus. These cells possess CD3 proteins in the cytoplasm but not on the surface, thus making intracellular CD3 (icCD3) a marker for thymus-derived ILCs. Indeed, icCD3+ ILC subsets have been detected in the lung and small intestine. Interestingly, the production of icCD3+ ILC1s and to a lesser extent, ILC3s depends on Tcrd but that of icCD3+ ILC2s does not. This prompted us to propose that ILC differentiation in the thymus involves Tcrd-dependent and independent mechanisms. The purpose of this application is to study how thymus-derived ILCs are generated and to investigate the functions of these cells. There are three aims. Aim1 will test the hypothesis that developing T cells with non-productive TCR gene rearrangement contributes to multipotent ILC precursors and immature γδ T cells gives rise to ILC1- or ILC3- biased precursors after down-regulation of their TCRs. We will employ approaches such as in vitro differentiation cultures and analyses of TCR gene rearrangement events. Aim2 will characterize icCD3+ ILCs in the small intestine by examining the age-dependent differentiation of ILC1s and ILC2 in relationship to T cell development and changes in gut microbiota, and by comparing the type 1 responses of icCD3+ ILC1s to those of conventional ILC1s and NK cells as well as γδ T cells. Aim3 will investigate the interplay of type 2 and type 3 immune responses and compare the behaviors of icCD3+ ILC2s to their icCD3- counterparts. Taken together, these studies may make conceptual advancement in developmental immunology and shed light on the contribution of thymus-derived ILCs to age-related differences in immunity.


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 = -$438 )
2026	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	2	2/18/2026	TERMINATION	-$438
														Subtotal = -$438

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	2	4/18/2025	TERMINATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $682,186 )
2024	2024	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	2	6/14/2024	NON-COMPETING CONTINUATION	$682,186
														Subtotal = $682,186

Issue Date FY: 2023 ( Subtotal = $691,734 )
2023	2023	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	000	1	7/19/2023	NEW	$691,734
2023	2023	OKLAHOMA MEDICAL RESEARCH FOUNDATION	825 NE 13TH ST	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Allergy and Infectious Diseases Research	001	1	8/29/2023	NEW	$0
														Subtotal = $691,734

Grand Total All Awards = $1,373,482

Top

All Categories

About

Search

Reports

Data Submission

Award Information

γδTCR-dependent and independent differentiation of innate lymphoid cells

Award Number: R01AI178947

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: 07/20/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2025

AWARD TERMINATION DATE: 04/18/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer