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Content archived on 2024-05-30

The roles of innate lymphoid cells and rhinovirus in asthma exacerbations

Objective

Asthma exacerbations represent a high unmet medical need in particular in young children. Human Rhinoviruses (HRV) are the main triggers of these exacerbations. Till now Th2 cells were considered the main initiating effector cell type in asthma in general and asthma exacerbations in particular. However, exaggerated Th2 cell activities alone do not explain all aspects of asthma and exacerbations. Building on our recent discovery of type 2 human innate lymphoid cells (ILC2) capable of promptly producing high amounts of IL-5, IL-9 and IL-13 upon activation and on mouse data pointing to an essential role of these cells in asthma and asthma exacerbations, ILC2 may be the main initiating cells in asthma exacerbations in humans. Thus we hypothesize that HRV directly or indirectly stimulate ILC2s to produce cytokines driving the effector functions leading to the end organ effects that characterize this debilitating disease. Targeting ILC2 and HRV in parallel will provide a highly attractive therapeutic option for the treatment of asthma exacerbations. In depth study of the mechanisms of ILC2 differentiation and function will lead to the design effective drugs targeting these cells; thus the first two objectives of this project are: 1) To unravel the lineage relationship of ILC populations and to decipher the signal transduction pathways that regulate the function of ILCs, 2) to test the functions of lung-residing human ILCs and the effects of compounds that affect these functions in mice which harbour a human immune system and human lung epithelium under homeostatic conditions and after infections with respiratory viruses. The third objective of this project is developing reagents that target HRV; to this end we will develop broadly reacting highly neutralizing human monoclonal antibodies that can be used for prophylaxis and therapy of patients at high risk for developing severe asthma exacerbations.

Fields of science (EuroSciVoc)

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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.

Call for proposal

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ERC-2013-ADG
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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.

ERC-AG - ERC Advanced Grant

Host institution

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
EU contribution
€ 2 499 593,00
Address
MEIBERGDREEF 15
1105AZ Amsterdam
Netherlands

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Region
West-Nederland Noord-Holland Groot-Amsterdam
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

No data

Beneficiaries (1)

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