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Nutritional Retinoic Acid as an early cDC2A fate instructive signal in the bone marrow

Project description

Retinoic acid and dendritic cell development

Retinoic acid (RA) is a metabolite of vitamin A, which plays an essential role in regulating immunity by influencing the differentiation and function of immune cells. With the support of the Marie Skłodowska-Curie Actions programme, the cDcIVA project aims to investigate the role of RA in immune responses, especially in the communication axis between the gut and the bone marrow. Researchers will focus on how RA shapes the fate of conventional dendritic cell (cDC) precursors in the bone marrow and boosts cDC output. In addition, they will identify the bone marrow niches that supply RA and advance knowledge with implications for vaccination and cancer immunotherapy.

Objective

cDcIVA aims to reveal a gut-bone marrow axis mediated by retinoic acid (RA) as a fate-instructive factor for the development of conventional dendritic cell (cDC) precursors in the bone marrow. Communication between the intestine and other organs, such as the bone marrow is mediated by several nutrients, including Vitamin A. This proposal focuses on examining how the Vitamin A derivative, RA, reaches the bone marrow and boosts the output of a specific RA-responsive cDC subset with implications on predisposing certain effector functions of the adaptive immune system. By integrating in vitro differentiation assays, spatial transcriptomics, and in vivo RA manipulations (genetically and pharmacologically), this proposal aims to: 1) establish the role of Vitamin A, as a mediator of the gut-bone marrow axis, in regulating cDC development, 2) demonstrate that retinoic acid is the sole Vitamin A metabolite that can have cell intrinsic effects on cDC progenitors and 3) reveal the cells that metabolise and supply RA to cDC progenitors and form part of an instructive bone marrow niche. cDcIVA will advance our understanding of how the interplay between nutrition and immunity can regulate the development of the cells that govern the effector functions of the adaptive immune system, offering valuable insights for future research in vaccination and cancer immunotherapy.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

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

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Coordinator

FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Net EU contribution
€ 191 343,12
Address
AVENIDA BRASILIA, CENTRO DE INVESTIGACAO DA FUNDACAO CHAMPALIMAUD
1400-038 LISBOA
Portugal
Activity type
Research Organisations
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Total cost
No data