Objective
Transforming growth factor-beta (TGF-b) plays a critical role in maintaining gut immune homeostasis. Although ubiquitously expressed, TGF-b must be activated in order to enable subsequent signaling. TGF-b activation thus represents a major point of regulation of intestinal immune responses.
I have shown that expression of alpha-v-beta-8 integrin (avb8) by dendritic cells (DCs) is required to activate TGF-b so that it can signal to T cells. Furthermore, I have shown that avb8 expression is restricted to intestinal CD103+ DCs. However the mechanisms by which avb8 expression, and thus the ability to activate TGF-b, is restricted to this subset of DCs are unknown.
In this fellowship, I propose (1) to define the mechanisms by which avb8 expression is regulated in DCs, and (2) to determine whether avb8 expression program can be manipulated in order to control intestinal inflammation.
These studies will provide a detailed understanding of how DCs acquire a key immune-regulatory function, the activation of TGF-b. Furthermore, they will explore whether this is disrupted in patients with Inflammatory Bowel Diseases (IBD) and if avb8 expression can be manipulated in DCs. Together, this will provide new information on how intestinal homeostasis is established, and open new areas of research for the development of IBD treatment.
The increase in IBD and the chronic and debilitating nature of these disorders emphasize the relevance of a better understanding of the processes that underlie normal regulation of mucosal immune responses. The implementation of this proposal will build on both the expertise of the Host Institution and the transfer of unique know how and tools by the Applicant from Harvard Medical School. This transfer includes both reagents and collaborations I developed during my postdoctoral experience. Thus this proposal will develop long-lasting cooperation between leading US-Research center and contribute to increasing European excellence and competitiveness.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-IIF
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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.
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.
Coordinator
75794 PARIS
France
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.