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Deciphering autoreactive T cell immunity in human inflammatory peripheral neuropathies.

Objective

Guillain-Barré syndrome (GBS) is a rare heterogenous inflammatory peripheral neuropathy usually triggered by a preceding infection and causing a potentially life-threatening progressive muscle weakness. While the disease is generally considered to have an autoimmune basis, the underpinning immune-mediated mechanisms remain mostly elusive. This aspect poses a significant medical challenge in terms of accurate diagnosis, prognosis, and treatment. Building on our recent findings revealing that autoreactive T cell immunity play a key role in a subset of GBS patients, the project proposed herein aims at systematically elucidating its relative contribution to distinct GBS subtypes and disease stages. To this end, we will use cutting-edge technical approaches that enable the study of potentially rare autoreactive T cells in human biological samples (i.e. blood, cerebrospinal fluid and tissue biopsies) through three specific aims: Aim 1 is to perform in-depth immunophenotyping of blood-circulating immune cells for identification of potential variations in their frequency and distribution across GBS subtypes and stages; Aim 2 is to provide a systematic characterization of self-reactive T cells in patients’ biological samples by combining in vitro T cell screenings and ex vivo tetramers staining with high-throughput single cell analysis, such as single T cell clone generation, single cell RNA sequencing and TCR sequencing; Aim 3 is to dissect the cellular and molecular bases of cross-reactive T cell immunity in GBS by integrating in vitro sequential stimulation, single T cell clone generation and TCR sequencing with mass spectrometry-based immunopeptidomics or lipidomics. The outcomes of this project will significantly expand our understanding of the immunopathology of inflammatory peripheral neuropathies and advance our basic knowledge of human autoreactive T cell biology, with substantial implications for biomedical applications.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-COG

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Host institution

UNIVERSITA VITA-SALUTE SAN RAFFAELE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 000 000,00
Address
VIA OLGETTINA 58
20132 Milano
Italy

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Region
Nord-Ovest Lombardia Milano
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.

€ 2 000 000,00

Beneficiaries (1)

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