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Early life regulation of microbiota specific thymic T cell development

Award Number: R01AI173406
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: 11/07/2022
PERIOD OF PERFORMANCE END DATE: 10/31/2027

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Early life regulation of microbiota specific thymic T cell development - Project Summary Early life exposure to environments rich in microbial products corresponds with a more diverse microbiota and significantly decreases susceptibility to developing asthma and atopic sensitization. However, it is unclear how this early life exposure supports proper immune function. In recently published data, we find thymic expansion of microbiota specific T cells in early life. This is driven by microbiota carrying intestinal dendritic cells migration from the intestine to the thymus. We hypothesize specific microbial signals in intestinal environment in young mice, including signaling downstream of microbe attachment to intestinal epithelial cells, encourages intestinal DC trafficking to thymus. In the thymus, we hypothesize these microbes serve as a template to ensure expansion of microbe specific T cells, offering protection from pathogen challenge. Understanding these specific microbial derived signals, as well as unique thymic environmental cues during early life will allow us to understand this novel pathway. In Aim 1 of the proposed work, we will use in vivo models to understand the role for the intestine in this system, identifying molecular signals activating thymic migration of intestinal DCs. In Aim 2 we will determine the thymic signals that allow for thymic expansion of microbiota specific T cell. We will determine whether gut migratory APCs regulate selection or expansion of microbiota specific T cells. Finally, will determine whether migration is restricted by the age of the thymus or intestine environment through a series of thymic transplant studies. These mechanistic studies will help identify pathways that we will be able to manipulate to alter thymic T cell development and limit or rescue from the development of inflammatory disease.


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 = $817,057 )
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Allergy and Infectious Diseases Research	000	4	12/5/2025	NON-COMPETING CONTINUATION	$817,057
														Subtotal = $817,057

Issue Date FY: 2025 ( Subtotal = $792,545 )
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Allergy and Infectious Diseases Research	000	3	11/1/2024	NON-COMPETING CONTINUATION	$792,545
														Subtotal = $792,545

Issue Date FY: 2024 ( Subtotal = $817,057 )
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Allergy and Infectious Diseases Research	000	2	10/27/2023	NON-COMPETING CONTINUATION	$735,352
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Allergy and Infectious Diseases Research	001	2	5/13/2024	NON-COMPETING CONTINUATION	$81,705
														Subtotal = $817,057

Issue Date FY: 2023 ( Subtotal = $829,651 )
2023	2023	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Allergy and Infectious Diseases Research	000	1	11/7/2022	NEW	$829,651
														Subtotal = $829,651

Grand Total All Awards = $3,256,310

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Early life regulation of microbiota specific thymic T cell development

Award Number: R01AI173406

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: 11/07/2022

PERIOD OF PERFORMANCE END DATE: 10/31/2027

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