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Characterizing Microbe-specific Immune Responses in the pathogenesis of Autoimmunity

Objective

Dysregulation in the balance of CD4+ T helper cell populations can severely alter susceptibility to a number of chronic inflammatory diseases, including inflammatory bowel disease (IBD). The incidence of IBD is dramatically increasing in Europe and worldwide and its therapy represents an important unmet medical need, since a significant proportion of patients fail to respond to currently available immunotherapies. Therefore, a better characterization of the immunological events underlying each form of IBD is of foremost importance. Increasing evidence points to the pivotal role of a dysregulated mucosal immune response to the intestinal microbiota in the pathogenesis of IBD. However, little is known about the mechanisms contributing to the generation of commensal-specific adaptive immune responses, and whether their differential localization can shape severity and anatomical extent of the disease. Indeed, the intestines comprise anatomically distinct regions that are exposed to different luminal antigens and this diversity eventually determines a regionalization of intestinal immune functions and microbiota-specific T cell responses. The aim of this proposal is to deeply characterize microbiota-specific T cell responses generated under different inflammatory conditions, in terms of differentiation, plasticity, heterogeneity, function and homing potential. To this aim, the proposed work will combine the use of CBir1 TCR transgenic mice, whose T cells recognize a microbial antigen that is immunodominant in IBD patients, and cutting-edge techniques such as single-cell RNA sequencing.
By modelling the microbiota-specific immune response in vivo in the context of gut inflammation, I will characterize the function and homing properties of microbiota-specific T cells at the population and single-cell level, aiming at identifying new therapeutic targets for the treatment of localized forms of gut inflammation.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

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

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

KAROLINSKA INSTITUTET
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.

€ 173 857,20
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
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.

€ 173 857,20
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