Tuesday, February 17, 2026 2/17/2026

Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation

Award Number: R01HL158926
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation - PROJECT SUMMARY Inhalation of aerosolized dusts from urban, rural, and farming environments can trigger harmful airway inflammation and injury; over time, continual exposure to these particulates increases one’s risk for developing inflammatory airway diseases. While dust exposures negatively impact lung health, factors contributing to protection versus susceptibility to lung disease following these continual inhalational exposures are unclear. A recently discovered class of specialized pro-resolving lipid mediators (SPM) derived from omega-3 fatty acids regulate lung inflammation, immunity, and repair, and are likely key to the beneficial effects of diets high in omega-3 fatty acids. Our previous investigations identified that the omega-3 fatty acid docosahexaenoic acid (DHA) and its lipid metabolite maresin-1 (MaR1) mitigate airway inflammation from acute and repetitive organic dust exposure, mediated in part by macrophage activation and pro-repair activities on the airway epithelium. Our exciting new data identify that omega-3 fatty acids and MaR1 can activate IL-22 signaling in lung macrophages. IL-22 signaling promotes mucosal immunity and epithelial barrier integrity, and its activation in the presence of these bioactive lipids may be key to their protective effects. Furthermore, our novel finding of IL-22 signaling in macrophages challenges current dogma regarding the activation and regulation of this pathway. The goal of this proposal is to investigate the role of omega-3 fatty acids in promoting pro-repair IL-22 signaling in the lung following dust exposures. We hypothesize that omega-3 fatty acids and SPM promote lung recovery following particulate matter exposures by inducing alveolar macrophage IL-22 production that subsequently promotes alveolar macrophage pro-resolution polarization and lung epithelial repair. To test this hypothesis, in Aim 1, we will establish the impact of omega-3 fatty acids and IL-22 on lung recovery following dust exposure. In Aim 2, we will evaluate the role of omega-3 fatty acids and IL-22 in epithelial repair and mucosal immunity during dust exposure. In Aim 3, we will identify how SPM and IL-22 signaling impacts lung macrophage polarization. Together, our studies will identify how omega-3 fatty acids modulate susceptibility versus resilience to dust exposures, including a novel protective mechanism via activation of macrophage IL22 signaling to promote tissue repair and mucosal immunity. We expect our studies’ findings to guide novel treatment strategies for lung 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 = $0 )
2026	2024	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	000	5	2/11/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $447,889 )
2025	2025	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Lung Diseases Research	003	6	9/22/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$447,889
2025	2024	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	004	5	9/23/2025	OTHER REVISION	$0
2025	2024	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	001	5	7/16/2025	OTHER REVISION	$0
2025	2024	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	000	5	6/4/2025	TERMINATION	$0
2025	2024	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	002	5	9/22/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $447,889

Issue Date FY: 2024 ( Subtotal = $523,511 )
2024	2024	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	001	5	7/30/2024	SUPPLEMENT FOR EXPANSION	$72,003
2024	2024	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	000	5	7/11/2024	NON-COMPETING CONTINUATION	$451,508
														Subtotal = $523,511

Issue Date FY: 2023 ( Subtotal = $535,380 )
2023	2023	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	001	4	8/24/2023	SUPPLEMENT FOR EXPANSION	$67,235
2023	2023	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	000	4	6/30/2023	NON-COMPETING CONTINUATION	$468,145
														Subtotal = $535,380

Issue Date FY: 2022 ( Subtotal = $461,524 )
2022	2022	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	002	3	6/3/2022	NON-COMPETING CONTINUATION	$461,524
2022	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	000	2	4/18/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$490,346
2022	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Lung Diseases Research	003	1	6/15/2022	NEW	-$1
2022	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Lung Diseases Research	004	2	6/15/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
2022	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Lung Diseases Research	001	1	4/19/2022	NEW	-$490,346
														Subtotal = $461,524

Issue Date FY: 2021 ( Subtotal = $490,347 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Lung Diseases Research	000	1	6/30/2021	NEW	$490,347
														Subtotal = $490,347

Grand Total All Awards = $2,458,651

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Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation

Award Number: R01HL158926

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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