Summary
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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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/898090 |
| Start date: | 01-07-2020 |
| End date: | 30-06-2022 |
| Total budget - Public funding: | 178 320,00 Euro - 178 320,00 Euro |
Cordis data
Original description
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.Status
CLOSEDCall topic
MSCA-IF-2019Update Date
28-04-2024
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