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Functional Organization of Immunity by Lymphoid Stromal Cells

Project description

The role of lymph node stromal cells in immunity

Undoubtedly, the immune system has a very challenging job, having to provide tailored immunity while evading destruction to self. Emerging evidence indicates an important role for lymphoid organ stromal cells in the quality and quantity of the immune response. The aim of the EU-funded Stroma.Org project is to understand how these cells support immunity at the molecular and cellular level. For this purpose, scientists will combine different methodologies to generate a single-cell atlas of lymph nodes. They will also investigate if lymph node cell organisation is altered in asthma since such a change could explain the increased immunity to harmless allergens.

Objective

The immune system is faced with a substantial challenge – it must provide rapid, tailored immunity to the host without a priori knowledge of when, where and which pathogen will invade, and at the same avoid damage to self. Recent evidence, including my own prior work, suggests that the anatomical organization of the lymphoid organ in which the immune response is initiated determines the quality and quantity of the response. Lymph nodes (LNs) are supported by a scaffold of mesenchyme-derived stromal cells (SCs) that not only provides gross anatomical support, but also produces critical survival factors and localization/movement guidance cues to antigen-presenting cells and antigen-responsive lymphocytes during the initiation of the immune response. Despite the now emerging role of SCs in immune responsiveness, it is unclear at a molecular and cellular level how these cells support the fine-grained spatial and temporal requirements for robust immunity. Here, using novel single cell datasets, advanced highly-multiplex immunofluorescence imaging, spatial statistics, genetic targeting and in house-developed tools to track the development of immune responses, I aim to 1) create a comprehensive single cell atlas of LN organization in homeostasis, 2) unravel the rules of lymphoid SC specification and organizer function, 3) determine the impact of LN architecture on protective immunity, and 4) determine how such organization is altered in asthma, a highly prevalent chronic inflammatory airway, since alterations in SC-immune cell intercellular communication could explain increased immunity to harmless allergens, in the face of reduce immunity to viral infection and vaccination. By combining my qualifications in SC biology and LN organization with the expertise of the host lab in lung immunopathology, I have created an ambitious work plan that will serve as critical foundation to design future therapeutic interventions that benefit human health.

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

VIB VZW
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.

€ 178 320,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
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.

€ 178 320,00
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