EXODUS
Financiado
Light induced spatially EXact and genetically encoded labeling of immune cells f...
Light induced spatially EXact and genetically encoded labeling of immune cells for monitoring of lOng Distance and Ultra compartment Shuttling during autoimmunity and chronic inflammation
The incidence of autoimmune diseases including multiple sclerosis is dramatically increasing. While there is a genetically defined bedrock susceptibility to develop T cell mediated autoimmunity, environmental cues likely determine...
The incidence of autoimmune diseases including multiple sclerosis is dramatically increasing. While there is a genetically defined bedrock susceptibility to develop T cell mediated autoimmunity, environmental cues likely determine the threshold for disease development. Yet, little is known on how environmental cues sensed at body/environment interfaces are translated into immunopathology in distant organs like the central nervous system (CNS).
Here, we raise the hypothesis that immune cells must be activated at epithelial surfaces and then physically migrate to distant organs in order to induce autoimmunity. Furthermore, we propose that the state of activation of (either lymphoid or myeloid) immune cells can be interrogated by IL-6 production since IL-6 deficiency confers resistance to virtually any organ specific autoimmune disease and we have contributed fundamentally in defining the role of IL-6 for the generation of Th17 cells that are highly associated with autoimmune tissue inflammation.
In EXODUS, we will develop ground-breaking next generation reporter tools in order to test these hypotheses. A split Cre recombinase protein, which dimerizes and is activated by blue light, will be used to genetically label cells (and their progeny) in a topologically defined manner (compartment reporter). Furthermore, we have developed a novel type of Cre-inducible in vivo IL-6 reporter (activation reporter). The combination of these tools will enable us to trace the anatomical compartment of activation of immune cells without limitations in lag time.
Thus, site specific photogenetic co-induction of a fluorescence and IL-6 reporter will be used to probe peripheral sites for their potency to licence immune cells to travel to the CNS (Forward). Vice versa, labeling of cells in the CNS (through a thinned skull window) will allow for studying immune cell exodus from the CNS in homeostasis and during inflammation (Reverse).
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Duración del proyecto: 70 meses
Fecha Inicio: 2015-07-09
Fecha Fin: 2021-05-31
Fecha Fin: 2021-05-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-05-31
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-CoG-2014:
ERC Consolidator Grant
Cerrada
hace 10 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIV...
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Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
253.99K€ |
Participante