NEMESIS · Neuron/mast cell interactions in skin diseases
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-07-01 → 2019-06-30
- EU contribution
- €185,076
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Neuron/mast cell interactions in skin diseases
The atopic dermatitis. Atopic dermatitis (AD) also known as eczema is a chronic itch inflammatory skin disease that affects one in ten people. Moderate-to severe AD may have a strong impact on health-related quality of life, especially due to itch burden. AD is frequently associated with atopic comorbidities such as asthma and allergic rhinitis. The etiology of AD is incompletely understood, but many factors (i.e., complex interactions between environmental and genetic factors, involvement of various types of immune or structural cells and multiple signaling pathways) are thought to contribute to the development of skin lesions in AD. There are accumulating evidences showing that cutaneous sensory neurons play a critical role in such diseases. This project aims to investigate a potential new therapeutic target in the prevention and treatment of allergic skin inflammation: the interactions between specific nociceptors (nerves that sense damaging stimuli by sending signals to the spinal cord and brain) and type 2 immunity. Objectives. Aim 1. Elucidate the role of nociceptors in the development of AD-like pathology. Aim 2. Identify the role of nociceptor/immune cell cross-talk in the development of AD-like pathology. Aim 3. Test the impact of nociceptor/immune cell cross-talk on skin barrier function.
Data: CORDIS, © European Union
Project objective
Atopic dermatitis (AD) is a chronic skin inflammatory disease affecting 10-20% of children worldwide. The etiology of AD is incompletely understood, but many elements (e.g., genetic, environmental or immune) are thought to contribute to the pathogenesis. The skin is specifically enriched in mast cells (MCs) and innervated by a network of abundant sensory neurons. New findings suggest that nociceptive sensory neurons (nociceptors) might regulate the development of immune responses. Skin MCs also express a transcriptional signature of genes encoding neuropeptide receptors (e.g., Mrgprb2: the receptor for the substance P [SP]), through which MCs might uniquely interact with nociceptors. Based on solid preliminary data, the central hypothesis of this project is that SP-producing nociceptor/Mrgprb2+ MC interactions play a critical role in AD pathogenesis. Using a relevant mouse model of AD and innovative imaging approaches, we now aim to elucidate [1] which subset(s) of nociceptor is involved in AD, [2] how SP+ nociceptor/Mrgprb2+ MC interact in our model and in skin lesions from patients diagnosed with AD and [3] how such interactions might favor skin barrier dysfunction. This project promises to provide new insights into skin neuro-immune interactions and may lead to the discovery of new therapeutic targets to treat AD pathology.
Original text from CORDIS.
Participants
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union