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Content archived on 2024-05-28

Dissecting the human T cell response to pathogens, allergens, and self-antigens

Objective

The overall goal of this project is to test, in the human system, several hypotheses related to the role of T helper (Th) subsets in immunity and immunopathology. Using an experimental approach that takes advantage of high throughput culture methods and combines the ex vivo analysis of memory T cells with the in vitro priming of naïve T cells, we will dissect the Th cell response to pathogens, allergens, and self-antigens, in terms of antigen-specificity, tissue tropism, and cytokine production. We will identify signals and pathways triggered by microbes and allergens that prime polarized Th1, Th2, Th17 and Th22 cells as well as T cells with hybrid phenotypes producing, for instance, IFN-γ and IL-17 or IL-4 and IL-22. We will also address fundamental questions related to tolerance and autoimmunity by measuring frequency and distribution of self-reactive T cells in healthy donors and patients. The analysis of the response to microbes and allergens will address the possibility that different antigens, depending on abundance or location, may drive divergent Th cell responses, thus shedding light on the mechanisms of polarization and immunodominance in vivo. In pilot studies the project will also translate basic findings to the clinical setting, linking polarized Th responses to disease state and severity. Finally, using lentiviral-based approaches for gene silencing and overexpression, we will perform mechanistic studies to understand how environmental factors modulate in Th cells the production of pro- and anti-inflammatory cytokines. The hypotheses tested are strongly supported by preliminary observations from our own laboratory as well as from the biomedical literature. We expect that these studies will significantly expand our basic understanding of T cell biology and will have translational implications for the definition of correlates of protection or disease activity and for the design of improved vaccination and therapeutic strategies.

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

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2012-ADG_20120314
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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

FONDAZIONE PER L'ISTITUTO DI RICERCA IN BIOMEDICINA
EU contribution
€ 2 495 200,00
Address
VIA FRANCESCO CHIESA 5
6500 Bellinzona
Switzerland

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Region
Schweiz/Suisse/Svizzera Ticino Ticino
Activity type
Research Organisations
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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.

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Beneficiaries (1)

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