Descripción del proyecto
Contribución de la interferencia neuroinmunológica a la respuesta inmunitaria mucosa
Los estímulos internos y externos son reconocidos por los sistemas nervioso e inmunitario del cuerpo. La integración de las señales de estímulos y la obtención de respuestas adecuadas son fundamentales para mantener la homeostasis. Sin embargo, todavía se desconocen los mecanismos implicados en este proceso. En el proyecto ENTRI, financiado con fondos europeos, proponen crear un nuevo método genético y herramientas para la investigación de la interferencia neuroinmunológica en las superficies mucosas, mediante el uso de distintos modelos de enfermedades. El estudio permitirá la evaluación selectiva de la expresión génica y la función de la respuesta neuronal e inmunitaria, permitiendo así comprender mejor la forma en que la interferencia neuroinmunitaria contribuye a la inmunidad a los parásitos o el desarrollo de alergias. Este proyecto podría dar lugar a un concepto general de regulación inmunitaria mucosa.
Objetivo
Environmental and internal stimuli are constantly sensed by the body’s two large sensory units, the nervous system and the immune system. Integration of these sensory signals and translation into effector responses are essential for maintaining body homeostasis. While some of the intrinsic pathways of the immune or nervous system have been investigated, how the two sensory interfaces coordinate their responses remains elusive. We have recently investigated neuro-immune interaction at the mucosa of the intestine, which is densely innervated by the enteric nervous system (ENS). Our research has exposed a previously unrecognized pathway used by enteric neurons to shape type 2 immunity at mucosal barriers. Cholinergic enteric neurons produce the neuropeptide Neuromedin U (NMU) to elicit potent activation of type 2 innate lymphoid cells (ILC2s) via Neuromedin U receptor 1, selectively expressed by ILC2s. Interestingly, NMU stimulated protective immunity against the parasite Nippostrongylus brasiliensis but also triggered allergic lung inflammation. Therefore, the NMU-NMUR1 axis provides an excellent opportunity to study how neurons and immune cells interact to regulate immune responses and maintain body homeostasis. We propose to generate and use elegant genetic tools, which will allow us to systematically investigate the consequences of neuro-immune crosstalk at mucosal surfaces in various disease models. These tools will enable us to selectively measure and interfere with neuronal and ILC2 gene expression and function, thereby leading to an unprecedented understanding of how the components of neuro-immune crosstalk contribute to parasite immunity or allergic disease development. Furthermore, we will progress into translational aspects of NMU-regulated immune activation for human immunology. Therefore, our research has the potential to develop basic concepts of mucosal immune regulation and such discoveries could also be harnessed for therapeutic intervention.
Ámbito científico
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Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
10117 Berlin
Alemania