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Local and systemic mechanisms for metabolic inflammation chronicity

Objective

Chronic inflammation underlies several diseases and is a common basis of multiple comorbidities. In obesity, chronic inflammation of the adipose tissue (AT) and liver contributes to the metabolic syndrome and related metabolic-inflammatory pathologies. Here, we propose a thorough and innovative approach to revolutionize understanding of metabolic inflammation chronicity. We will address both local (at the respective tissue level) and systemic mechanisms, involving the novel principle of trained innate immunity (TII) and inflammatory adaptation of the bone marrow (BM). (i) Local: In chronic metabolic inflammation, there is an imbalance between chronic accumulation/activation of inflammatory cells and resolution of inflammation (RoI) in favor of the former. Based on our recent findings regarding integrin-dependent chronic macrophage retention in the obese AT and that Developmental endothelial locus-1 promotes RoI, we will here identify novel pathways towards counter-acting chronicity of metabolic inflammation and facilitating its resolution and test their therapeutic efficacy. (ii) Systemic: Systemic metabolic/inflammatory feedback to the BM may trigger long-term adaptations of hematopoietic progenitors, fueling a feed-forward loop of perpetual inflammation. Following our discovery that TII is initiated in the BM, we will pursue the hypothesis that maladaptive training of BM progenitors in obesity facilitates metabolic inflammation chronicity, via generation of myeloid cells with higher potential for tissue accumulation and inflammatory activation, and promotes development of obesity-related inflammatory comorbidities. Despite apparent links, local and systemic mechanisms are mostly studied independently of each other rather than through an integrative approach, which will be followed here for the first time. Our proposal will lead to breakthrough concepts in metabolic inflammation chronicity and to novel therapeutic strategies for metabolic-inflammatory pathologies.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2021-ADG

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Host institution

TECHNISCHE UNIVERSITAET DRESDEN
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.

€ 2 493 275,00
Address
HELMHOLTZSTRASSE 10
01069 Dresden
Germany

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Region
Sachsen Dresden Dresden, Kreisfreie Stadt
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.

€ 2 493 275,00

Beneficiaries (1)

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