Project description
The role of dermal nociceptors in the pathophysiology of atopic dermatitis
Skin homeostasis is maintained through a delicate equilibrium between keratinocytes, immune cells and the environment. Disruption of this interplay may lead to skin inflammation, such as atopic dermatitis (AD). The EU-funded IMMCEPTION project is investigating how dermal nociceptors that receive noxious stimuli and deliver the signals to the brain and spinal cord may be implicated in the immune response. Using a mouse model of AD and sophisticated in vivo imaging approaches, researchers will study the interaction of nociceptors with skin mast cells. Extrapolation of these findings in human cells will uncover important information on the pathophysiology of AD.
Objective
Preserving skin homeostasis depends on complex interactions among structural cells, immune cells, and the environment. Dysregulation of this delicate equilibrium contributes to the development of type 2 immunity-associated skin inflammation (i.e. allergic skin inflammation), including atopic dermatitis (AD). The skin is a complex organ harboring various tissue-resident immune cells (e.g. dendritic cells, mast cells and macrophages) and innervated by a meshwork of sensory nerves, including those involved in nociception (i.e. nociceptors), which respond to injurious or potentially damaging stimuli by transmitting signals to the spinal cord and brain. Despite their role in the transmission of sensation, recent evidences have suggested that nociceptors could be powerful regulators of ongoing immune response.
We wish to use sophisticated mouse models and new in vivo imaging approaches to define the roles of subsets of dermal nociceptors, cationic neuropeptide substance P, dermal mast cells expressing the recently discovered receptor for cationic molecules Mas-related G protein-coupled receptor b2 (i.e. Mrgprb2), in a mouse model of AD that has many pathological, immunological, and gene expression similarities with the corresponding human disorder. We also will define the translational relevance of our mouse studies by performing parallel analyzes of nociceptors and mast cells in the lesional skin of patients from USA and France with clinically-established AD. To accomplish these goals, we have proposed herein a body of work that is solidly based on our preliminary data, with four Aims that will test innovative hypotheses by using informative genetic approaches, as well as new intravital imaging systems we recently developed.
This work thus will address significant gaps in our knowledge about the pathophysiology of AD and has the potential to identify such neuro-immune interactions as a promising new therapeutic target in AD and perhaps other allergic 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: The European Science Vocabulary.
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.
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences basic medicine physiology homeostasis
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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)
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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)
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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.
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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-STG - Starting Grant
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Call for proposal
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(opens in new window) ERC-2018-STG
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75654 PARIS
France
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