Magnification of Asthma by human memory Group 2 Innate lymphoid Cells

Informations projet

MAGIC

N° de convention de subvention: 798927

DOI

10.3030/798927

Projet clôturé

Date de signature de la CE 9 Mars 2018

Date de début 1 Septembre 2018

Date de fin 31 Août 2020

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 177 598,80

Contribution de l’UE

€ 177 598,80

Coordonné par

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Netherlands

Periodic Reporting for period 1 - MAGIC (Magnification of Asthma by human memory Group 2 Innate lymphoid Cells)

Période du rapport: 2018-09-01 au 2020-08-31

Résumé du contexte et des objectifs généraux du projet

Allergen-sensitized individuals may develop chronic inflammation, typically found in asthmatic and atopic dermatitis patients. This process is thought to be mediated by the generation of antigen-specific memory Th2 cells, which respond stronger during subsequent encounters with the same allergen. The characterization of memory T cells has led to the development of vaccination therapies to produce desensitization towards specific antigens. However, these treatments are not always effective as some patients respond to a wide range of allergens in a non-specific manner. The causes for this non- specific allergic response are currently unknown.
This action postulates that Group 2 innate lymphoid cells, critical players in allergic inflammation, fill this gap of knowledge. The researcher showed that allergen-experienced mouse lung ILC2s acquire memory functions: remember previous allergen exposures and react stronger upon subsequent exposure to an unrelated allergen. The goal of this proposal is to demonstrate that human memory ILC2s are involved in atopic dermatitis exacerbation. The supervisor is an expert in human ILCs. Humanized mice will be used to define the phenotype and function of human memory ILC2 and the results will be further validated on peripheral blood and skin samples from healthy and atopic dermatitis patients.
Allergic diseases are highly prevalent worldwide with a substantial social and economic burden due to its high rate of under-diagnosis and under-treatment. Specific focus will be to raise awareness of clinicians and pharmaceutical companies about the potential of memory ILC2 as a target to improve diagnosis and treatment.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

We have analysed skin from healthy individuals and done phenotyping of ILCs by flow citometry. We aim to look for memory ILC2s. Functional in vitro assays suggest memory generation in dermal ILCs.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

scRNA sequencing on human dermal ILCs shows heterogeneity of ILCs. We aim to look for the memory ILC2 subpopulation. We will further correlate frequency of memory ILC2s with the severity of the symptoms on atopic dermatitis patients.

Human dermal ILC2 heterogeneity