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Dissecting the role of fatty acid oxidation in dendritic cell function and regulation of immune responses.

Project description

Cell metabolism and immune responses

Dendritic cells (DCs) orchestrate immune responses, acting as a bridge between innate and adaptive immunity. Notably, DCs have the unique ability to control both immune activation and maintain tolerance. Recent studies indicate that fatty acid oxidation can shape these immunological outcomes. With the support of the Marie Skłodowska-Curie Actions programme, the FADIR project will investigate the role of DC metabolism in cell behaviour across different tissues and health states. By combining immunological and biochemical tools, researchers aim to elucidate how metabolic activity within DCs dictates their role in the immune system. Project findings will advance our understanding of immune system regulation and pave the way towards the development of novel therapeutic strategies.

Objective

Conventional dendritic cells (cDCs) are pivotal regulators of the immune system capable of tilting immune responses towards effective immunity or tolerance. Over the last 15 years, an increasing body of work has highlighted how changes in the metabolic state of immune cells influence their functions. It has been shown that melanomas can promote cDC tolerogenic functions by augmenting mitochondrial fatty acid oxidation (FAO) via the β-catenin signalling pathway. Intriguingly, recent unpublished results in the host group suggest that boosting oxidative phosphorylation, a metabolic process closely related to FAO, increases cDC immunogenicity. Therefore, further work is required to delineate the relationship between mitchondrial metabolic adpatations and cDC tolerogenic and immunogenic functions. This action aims to further dissect the interconnection between FAO and cDC functions across different tissues both in steady-state and disease. To this end, I will use novel murine lines that allow for the modulation of FAO in cDCs and will combine classical immunology and biochemial assays to characterise cDCs both functionally and metabolically. This interdisciplinary approach will help us understand the relationship between metabolism and function in cDCs and how this affects the initiation of immune responses across tissues.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.)
Net EU contribution

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€ 194 074,56
Address
CALLE MELCHOR FERNANDEZ ALMAGRO 3
28029 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
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Research Organisations
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