Project description
Holistic investigation of metabolic inflammation chronicity mechanisms
Chronic inflammation (persistent overactivation of the body's immune response) underlies many serious diseases and is associated with metabolic syndrome in obesity. The ERC-funded LOSYSINCHRON project will investigate why metabolic inflammation becomes chronic, addressing both local and systemic mechanisms simultaneously for the first time. Furthermore, it will focus on its recent discovery that trained innate immunity is initiated in the bone marrow. Specifically, LOSYSINCHRON will study how inflammatory cells accumulate in fat tissue and liver when natural resolution processes fail, and how hematopoietic progenitors in the bone marrow become ‘mis-trained’ to perpetually overproduce cells with higher potential to promote metabolic inflammation. Insights are expected to shed new light on metabolic inflammation chronicity and open new therapeutic avenues for metabolic-inflammatory diseases.
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)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
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.
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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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.
01069 Dresden
Germany
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.