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The Differentiation and Function of heterogeneous populations of Allergen-specific Lung-resident Th2 CD4+ memory cells

Award Number: R01AI177874
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: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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The Differentiation and Function of heterogeneous populations of Allergen-specific Lung-resident Th2 CD4+ memory cells - Project Summary/Abstract Asthma is an inflammatory disease of the airways characterized by acute, intermittent and recurrent episodes of inflammation that can be induced by a specific allergen. CD4+ T cells contribute to this process by producing the Type 2 cytokines IL-4, IL-5, and IL-13 and inducing B cell production of IgE in response to T cell receptor (TCR) recognition of allergen peptides bound to MHCII molecules on host cells. In both murine models of disease and asthmatic patients, quiescent allergen peptide:MHCII (pMHCII)-specific CD4+ memory T cells can persist in lungs and lymphoid organs long after resolution of inflammation. Upon subsequent exposure to allergen, CD4+ memory T cells rapidly drive asthma-induced immunopathology making these cells attractive targets for allergen- specific immune modulation. Little is known, however, about the function and maintenance of Th2 memory cells that orchestrate the asthmatic response due to the challenge of tracking small populations of CD4+ T cells that express allergen pMHCII: specific TCRs. To address this lack of knowledge, we produced an MHCII tetramer containing a peptide from the Der p1 protein of the house dust mite (HDM), Dermatophagoides pteronyssinus, the most common cause of atopic asthma. Using this tetramer and a novel magnetic bead-based cell enrichment method of our design, we have found that IL-2 dependent, functionally heterogeneous populations of Th2 tissue resident memory cells reside in the lung for long periods of time. The central hypothesis of this application is that these distinct yet synergistic populations of Th2 “effector Trm” and B cell helping “Tfh Trm” contribute to asthma pathogenesis in unique ways. The goals of this proposal are to identify the molecular and cellular mechanisms that lead to Th2 Trm cell heterogeneity and determine how these cells persist in different regions of the lung. This innovative approach could provide the means for targeting specific pathologic functions of memory Th2 cells by immunotherapy or eliminating them altogether.


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 = $777,749 )
2026	2026	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	3	12/10/2025	NON-COMPETING CONTINUATION	$777,749
														Subtotal = $777,749

Issue Date FY: 2025 ( Subtotal = $841,731 )
2025	2025	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	2	3/11/2025	NON-COMPETING CONTINUATION	$841,731
														Subtotal = $841,731

Issue Date FY: 2024 ( Subtotal = $941,904 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	001	1	9/3/2024	NEW	$37,143
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	002	1	9/10/2024	NEW	$570,479
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	1	1/17/2024	NEW	$334,282
														Subtotal = $941,904

Grand Total All Awards = $2,561,384

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The Differentiation and Function of heterogeneous populations of Allergen-specific Lung-resident Th2 CD4+ memory cells

Award Number: R01AI177874

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: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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