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Monocyte-to-Macrophage Trajectories After Lung Injury: Spatio-temporal investigation, molecular regulation & functional implications for lung regeneration and immunity

Project description

The role of macrophages in lung injury and repair

During inflammation or infection, circulating monocytes are recruited to the lung tissue, where they differentiate into macrophages (InfMoMac) and contribute to pathogen clearance, inflammation and repair. Lungs also contain resident macrophages which are involved in tissue homeostasis and immune regulation. Understanding how these different cell subsets function after lung injury is central for lung immunity. The ERC-funded MoMacTrajectALI project will map the trajectories and functional diversities of InfMoMac in mouse models of lung injury. Researchers will analyse how intrinsic and extrinsic signals influence InfMoMac subpopulations and study their interactions in mouse and human lungs. Project findings will provide the foundation for new therapies.

Objective

The lung is particularly exposed to airborne and blood-borne insults. The mechanisms underlying lung tissue repair are therefore of fundamental biological importance and have critical implications for the prevention life-threatening inflammatory and tissue-damaging responses. Lung-resident tissue macrophages and inflammatory monocyte-derived macrophages (InfMoMac) are key players in the maintenance of homeostasis, repair responses and disease pathogenesis. Yet, to date, the complexity of lung macrophage responses after injury is far from being resolved. Here, we propose to explore InfMoMac trajectories and functional diversity in an unprecedented manner. To this end, we will use mouse models of infectious and non-infectious lung injury combined with single cell and spatial analyses, robust fate-mapping models and gene targeting approaches to investigate the spatio-temporal regulation, the subtissular niches, the intrinsic molecular programs and the extrinsic stress-, inflammation- and niche-related signals imprinting the identities and functions of InfMoMac subpopulations, and the functional consequences of the maintenance of InfMoMac for lung immunity to a subsequent challenge. Finally, we will investigate the interactions of InfMoMac with niche cells in humans by analyzing the InfMoMac landscape in human injured lungs and by studying a novel human embryonic stem cell-derived lung organoid model in co-culture with monocyte-derived cells. Based on robust preliminary data, sophisticated models and cutting-edge technologies, this ambitious project will increase our understanding of the basic mechanisms underlying the fine-tuning of InfMoMac trajectories in response to lung injuries and will thus provide robust foundations to manipulate their fate in medically relevant conditions such as severe respiratory viral infections and acute respiratory distress syndrome.

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-COG

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Host institution

UNIVERSITE DE LIEGE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 999 863,00
Address
PLACE DU 20 AOUT 7
4000 LIEGE
Belgium

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Region
Région wallonne Prov. Liège Arr. Liège
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 999 863,00

Beneficiaries (1)

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