Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation
Omega-3 脂肪酸诱导巨噬细胞 IL-22 信号传导,促进粉尘引起的肺部炎症的消退
基本信息
- 批准号:10834639
- 负责人:
- 金额:$ 6.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcidsAcuteAirway DiseaseAlveolar MacrophagesChronicDataDietDiseaseDocosahexaenoic AcidsDustEpitheliumExposure toFarming environmentGoalsImmunityInflammatoryInhalationInhalation ExposureInjuryInvestigationLeadLipidsLungLung diseasesMacrophageMacrophage ActivationMediatingMucosal ImmunityOmega-3 Fatty AcidsParticulateParticulate MatterPathway interactionsPredispositionProductionPulmonary InflammationRecoveryRegulationResolutionRiskRoleSignal TransductionTestingTimeUnited States National Institutes of Healthaerosolizedairway epitheliumairway inflammationdietaryepithelial repairinjured airwayinterleukin-22lipid mediatorlung healthnovelprotective effectrepairedresiliencerural environmenttissue repairtreatment strategyurban setting
项目摘要
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 IL-22 signaling to promote
tissue repair and mucosal immunity. We expect our studies’ findings to guide novel treatment
strategies for lung disease.
项目摘要
吸入来自城市、农村和农业环境的气溶胶粉尘可引发有害的
气道炎症和损伤;随着时间的推移,持续暴露于这些颗粒物会增加
患上炎症性气道疾病的风险。虽然灰尘暴露会对
肺健康,有助于保护的因素与肺疾病的易感性,
这些持续的吸入暴露尚不清楚。最近发现的一类特殊的
来自ω-3脂肪酸的促分解脂质介质(SPM)调节肺
炎症,免疫和修复,并且可能是高脂肪饮食有益效果的关键。
ω-3脂肪酸我们之前的调查发现,
二十二碳六烯酸(DHA)及其脂质代谢产物maresin-1(MaR 1)缓解气道
急性和反复接触有机粉尘引起炎症,部分由巨噬细胞介导
对气道上皮的活化和促修复活性。我们令人兴奋的新数据表明,
ω-3脂肪酸和MaR 1可以激活肺巨噬细胞中的IL-22信号传导。IL-22
信号传导促进粘膜免疫和上皮屏障完整性,并且其在
这些生物活性脂质的存在可能是其保护作用的关键。此外,我们的小说
巨噬细胞中IL-22信号传导的发现挑战了目前关于激活
和调节这一途径。这项提案的目的是调查欧米茄-3的作用
脂肪酸促进粉尘暴露后肺中的促修复IL-22信号传导。我们
假设omega-3脂肪酸和SPM促进了微粒吸入后肺恢复
通过诱导肺泡巨噬细胞产生IL-22,
促进肺泡巨噬细胞前分辨率极化和肺上皮修复。为了验证这一
假设,在目标1中,我们将确定ω-3脂肪酸和IL-22对肺的影响,
粉尘暴露后的恢复。在目标2中,我们将评估omega-3脂肪酸的作用,
IL-22在粉尘暴露后上皮修复和粘膜免疫中的作用在目标3中,我们将确定
SPM和IL-22信号传导如何影响肺巨噬细胞极化。我们的研究将
确定ω-3脂肪酸如何调节对灰尘暴露的敏感性与恢复力,
包括通过激活巨噬细胞IL-22信号传导促进
组织修复和粘膜免疫。我们希望我们的研究结果能够指导新的治疗方法
肺疾病的治疗策略
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Aspirin-Triggered Resolvin D1 Reduces Chronic Dust-Induced Lung Pathology without Altering Susceptibility to Dust-Enhanced Carcinogenesis.
- DOI:10.3390/cancers14081900
- 发表时间:2022-04-09
- 期刊:
- 影响因子:5.2
- 作者:
- 通讯作者:
Lipid-Sensing Receptor FFAR4 Modulates Pulmonary Epithelial Homeostasis following Immunogenic Exposures Independently of the FFAR4 Ligand Docosahexaenoic Acid (DHA).
- DOI:10.3390/ijms24087072
- 发表时间:2023-04-11
- 期刊:
- 影响因子:5.6
- 作者:Sveiven, Stefanie N.;Anesko, Kyle;Morgan, Joshua;Nair, Meera G.;Nordgren, Tara M.
- 通讯作者:Nordgren, Tara M.
IL-22 regulates inflammatory responses to agricultural dust-induced airway inflammation.
- DOI:10.1016/j.taap.2022.116044
- 发表时间:2022-07-01
- 期刊:
- 影响因子:3.8
- 作者:Ulu A;Sveiven S;Bilg A;Velazquez JV;Diaz M;Mukherjee M;Yuil-Valdes AG;Kota S;Burr A;Najera A;Nordgren TM
- 通讯作者:Nordgren TM
Diseased and healthy murine local lung strains evaluated using digital image correlation.
- DOI:10.1038/s41598-023-31345-w
- 发表时间:2023-03-20
- 期刊:
- 影响因子:4.6
- 作者:Nelson, T. M.;Quiros, K. A. M.;Dominguez, E. C.;Ulu, A.;Nordgren, T. M.;Eskandari, M.
- 通讯作者:Eskandari, M.
Agricultural dust derived bacterial extracellular vesicle mediated inflammation is attenuated by DHA.
- DOI:10.1038/s41598-023-29781-9
- 发表时间:2023-02-16
- 期刊:
- 影响因子:4.6
- 作者:Heires, Art J.;Samuelson, Derrick;Villageliu, Daniel;Nordgren, Tara M.;Romberger, Debra J.
- 通讯作者:Romberger, Debra J.
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Tara M Nordgren其他文献
Tara M Nordgren的其他文献
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{{ truncateString('Tara M Nordgren', 18)}}的其他基金
Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation
Omega-3 脂肪酸诱导巨噬细胞 IL-22 信号传导,促进粉尘引起的肺部炎症的消退
- 批准号:
10276478 - 财政年份:2021
- 资助金额:
$ 6.72万 - 项目类别:
Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation
Omega-3 脂肪酸诱导巨噬细胞 IL-22 信号传导,促进粉尘引起的肺部炎症的消退
- 批准号:
10441561 - 财政年份:2021
- 资助金额:
$ 6.72万 - 项目类别:
Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation
Omega-3 脂肪酸诱导巨噬细胞 IL-22 信号传导,促进粉尘引起的肺部炎症的消退
- 批准号:
10581016 - 财政年份:2021
- 资助金额:
$ 6.72万 - 项目类别:
Omega-3 fatty acids induce macrophage IL-22 signaling to promote resolution of dust-induced lung inflammation
Omega-3 脂肪酸诱导巨噬细胞 IL-22 信号传导,促进粉尘引起的肺部炎症的消退
- 批准号:
10634533 - 财政年份:2021
- 资助金额:
$ 6.72万 - 项目类别:
The role of omega-3 fatty acids and bioactive lipid signaling in airway inflammation and resolution following organic dust exposures
omega-3 脂肪酸和生物活性脂质信号在有机粉尘暴露后气道炎症和消退中的作用
- 批准号:
9769730 - 财政年份:2017
- 资助金额:
$ 6.72万 - 项目类别:
The role of omega-3 fatty acids and bioactive lipid signaling in airway inflammation and resolution following organic dust exposures
omega-3 脂肪酸和生物活性脂质信号在有机粉尘暴露后气道炎症和消退中的作用
- 批准号:
9547592 - 财政年份:2017
- 资助金额:
$ 6.72万 - 项目类别:
Effects of maresin-1 & organic dust on lung inflammation
maresin-1 的作用
- 批准号:
8649764 - 财政年份:2014
- 资助金额:
$ 6.72万 - 项目类别:
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