Objective
Pro-inflammatory cytokines play a crucial role in chronic inflammatory diseases. Focusing on spondyloarthritis (SpA), a prevalent and debilitating rheumatic condition characterized by inflammation and abnormal new bone formation, we demonstrated that TNF and IL-23/IL-17 inhibition potently blocks inflammation. However, these treatments have no proven effect on pathologic new bone formation and the resulting structural damage, indicating the unmet need for understanding upstream disease mechanisms. Immune cells, in particular myeloid cells, have been shown to be the major sources of TNF and IL-23 in experimental models. However, we and others failed to demonstrate abnormal cytokine production by myeloid cells in human SpA. What drives these pathogenic cytokines thus remains unknown.
We recently found that SpA synovial tissues contain an abnormal stromal population of myofibroblasts, that these myofibroblasts express TNF and IL-23 in vivo and in vitro when exposed to cellular stress, and that stromal expression of these cytokines does not only drive inflammatory responses in vitro but is required and sufficient to induce experimental SpA in vivo. Therefore, we propose that stressed stromal cells can act as primary drivers of cytokine-mediated tissue inflammation and remodelling. Using a translational approach - dynamic sampling of primary human target tissues, functional experiments ex vivo and in vitro, animal models, and targeted interventions in patients – we aim to unravel the role of stromal cells in SpA by defining: 1) the molecular profile of the stromal alterations, 2) the mechanisms of cytokine production by stromal cells, 3) the activation of downstream inflammatory pathways, 4) the role of stromal alterations in tissue remodeling, and 5) the contribution of stromal pathways to experimental and human SpA. Collectively, this project will allow to validate stromal cells as novel therapeutic targets for SpA and related disorders.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine rheumatology
- medical and health sciences health sciences inflammatory diseases
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics epigenetics
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - 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.
ERC-COG - Consolidator Grant
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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-2014-CoG
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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.
1105AZ Amsterdam
Netherlands
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.