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Local B cell memory in airway hypersensitivity.

Award Number: F31HL156459
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 09/30/2023

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Local B cell memory in airway hypersensitivity. - Project Summary/Abstract Allergic asthma is a chronic inflammatory disease of the airway that currently has no cure. Production of immunoglobulin E (IgE) to inhaled allergens drives inflammation and the allergic response seen in allergic asthma. Over half of patients exhibit allergen-specific IgE at the respiratory mucosa but not systemically in circulation, illustrating the importance of local production of IgE. However, the mechanisms that promote and maintain local pathogenic IgE responses are not understood. Using a mouse model of airway hypersensitivity, we have identified a population of memory B cells that localize to the lungs after repeated exposures to inhaled allergens. These lung-localized memory B cells exhibit specificity for allergens, persist after the resolution of inflammation, expand upon re-challenge with increase of local allergen-specific IgE. We hypothesize that tissue- resident memory B cells are the major source of local responses in asthmatic lungs, responsible for maintaining long-term hypersensitivity in the airway. In this proposal, we will elucidate the cellular environment that maintains lung residency of memory B cells in asthmatic lungs and investigate their functions in airway hypersensitivity. Specifically, in Aim 1, using in vivo depletion of circulating cells and parabiosis experiments we will verify the tissue-residency of memory B cells in asthmatic lungs. We will identify the potential niches of lung-localized memory B cells and examine the cellular environment responsible for their maintenance in the lungs using cutting-edge imaging technologies. In Aim 2, we will inhibit recruitment of circulating B cells during re-challenge and perform adoptive cell transfer of tissue-resident memory B cells to delineate the function of tissue-resident memory B cells in airway hypersensitivity. In summary, we aim to shed light on the fundamental biology of memory B cells in the respiratory tract and reveal their functions in airway hypersensitivity. This study may reveal a crucial cell population that can be targeted to treat or prevent the progression of allergic asthma in humans. This fellowship will provide the crucial support for the applicant to pursue a career as an independent investigator in immunology.


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: 2024 ( Subtotal = -$26,293 )
2024	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Lung Diseases Research	001	3	9/23/2024	NON-COMPETING CONTINUATION	-$379
2024	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Lung Diseases Research	000	3	8/22/2024	NON-COMPETING CONTINUATION	-$25,914
														Subtotal = -$26,293

Issue Date FY: 2023 ( Subtotal = $28,931 )
2023	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Lung Diseases Research	000	3	8/24/2023	NON-COMPETING CONTINUATION	$28,931
														Subtotal = $28,931

Issue Date FY: 2022 ( Subtotal = $32,513 )
2022	2022	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Lung Diseases Research	000	2	8/15/2022	NON-COMPETING CONTINUATION	$32,513
														Subtotal = $32,513

Issue Date FY: 2021 ( Subtotal = $31,797 )
2021	2021	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Lung Diseases Research	000	1	9/1/2021	NEW	$31,797
2021	2021	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Lung Diseases Research	001	1	9/1/2021	NEW	$0
														Subtotal = $31,797

Grand Total All Awards = $66,948

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Local B cell memory in airway hypersensitivity.

Award Number: F31HL156459

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 09/30/2023

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