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Neuropeptides and TRP receptors as effectors of Immune cell activation In IBD

Subject Area Gastroenterology
Term from 2015 to 2018
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 190140969
 
Little is known about molecular mechanisms of neuro-immune interactions in the gut. Increasing evidence suggests that the enteric nervous system plays an important role In IBD pathogenesis. The immunomodulatory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) are released from sensory neurons within the colonic wall. In previous studies we have shown that SP-deficient mice were completely protected in two models of experimental colitis. In contrast CGRP was rather protective. Molecular mechanisms underfying these effects are largely unknown. This project aims to investigate the effects of both neuropeptides on mucosal immunology in the context of expenmental colitis and human IBD. In various in vitro and in vivo assays TP10 will analyze neuropeptide-induced changes in lamina propna T cell and macrophage function In the context of colitis. This project will further clarify the role of TRP-receptors in neuronal and immune cell function in IBD. In neurons TRP channels control immunomodulatory neuropeptide release, however, some TRP channels are also constitutively expressed in various immune cell subtypes but their function there is only poorly understood. Translationalty, neuropeptide and TRP receptor expression and function will be evaluated in human samples of IBD patients and correlated to disease severity.
DFG Programme Clinical Research Units
 
 

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