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Dendritic cell navigation in lymphoid organs
FunderFrench National Research Agency (ANR)
Funder Contribution €355,978.00
DurationFrom 01 Jul 2024
Project codeANR-23-CE15-0043
Identifiers
Description
Conventional dendritic cells (cDC) are mononuclear phagocytes that decisively orchestrate adaptive immune responses. Within lymph nodes (LNs), they form dense and complex 3D networks allowing them to efficiently respond to immune challenges. Given the short life span and migratory activity of cDC, it is unclear how these networks are established and maintained over time. Using a new fate-mapping mouse model that tracks DC development, we have recently observed that DC precursors (preDC) enter via LN medullary cords rather than cortical high endothelial venules. These unique structures appear to act as topographical starting points for the differentiating cDC network and as local niches that regulates the speed of DC development, ultimately creating a cDC conveyor belt in LNs. While this concept is new and exciting, we are still missing a detailed understanding about how different mesenchymal cells and vascular components shape the maturation and positionning of cDC within lymphoid organs. By using in situ imaging in combination with innovative mouse models, in situ photoconversion, scRNAseq, and confocal microscopy, we will investigate (a) the role of specific stromal cell components (endothelial cells, fibroblasts) in regulating the maturation and positionning of cDCs in LN, the spleen and the thymus, and (b) the signals and molecules that control the navigation of these cells. Our studies will uncover key principles of cDC network regulation.
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Conventional dendritic cells (cDC) are mononuclear phagocytes that decisively orchestrate adaptive immune responses. Within lymph nodes (LNs), they form dense and complex 3D networks allowing them to efficiently respond to immune challenges. Given the short life span and migratory activity of cDC, it is unclear how these networks are established and maintained over time. Using a new fate-mapping mouse model that tracks DC development, we have recently observed that DC precursors (preDC) enter via LN medullary cords rather than cortical high endothelial venules. These unique structures appear to act as topographical starting points for the differentiating cDC network and as local niches that regulates the speed of DC development, ultimately creating a cDC conveyor belt in LNs. While this concept is new and exciting, we are still missing a detailed understanding about how different mesenchymal cells and vascular components shape the maturation and positionning of cDC within lymphoid organs. By using in situ imaging in combination with innovative mouse models, in situ photoconversion, scRNAseq, and confocal microscopy, we will investigate (a) the role of specific stromal cell components (endothelial cells, fibroblasts) in regulating the maturation and positionning of cDCs in LN, the spleen and the thymus, and (b) the signals and molecules that control the navigation of these cells. Our studies will uncover key principles of cDC network regulation.
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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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