Morphological and functional investigation of cross-talk between enteric neuron and dendritic cell

      The enteric nerve system, which is composed of sensory neurons, interneurons and motor neurons, integrally controls intestinal secretion and motility to maintain gut homeostasis. In addition, the intestine highly develops the mucosal immune system against pathogenic microorganisms. Recent studies show the involvement of gut microbiota in not only gastrointestinal disease such as irritable bowel syndrome and food allergy, but also psychiatric disorder such as autism spectrum disorders and Alzheimer’s disease. However, cross-talk between enteric neurons and immune cells in the intestine is still not fully understood. In this study, we focused on dendritic cells (DC), conductor cells in acquired immune responses, and morphologically and functionally investigated interactions between enteric neurons and DCs. Immunohistochemical analysis revealed that DCs (CD11c+ positive cells) were located in close proximity to enteric nerve fibers in the colonic mucosa of normal mice. Furthermore, enteric nerve fibers were decreased in the luminal surface of DSS-induced colitis mouse colon compared with normal mouse colon, but juxtaposed with DCs. Bone marrow-derived DCs (BMDCs) prepared from BALB/c mice using GM-CSF and enteric neurons isolated from the small intestine of BALB/c mice were co-cultured. The functional interaction was analyzed with Ca2+ imaging technique in the co-culture condition. Activation of enteric neurons with Na+ channel activator veratridine evoked an increase in intracellular calcium concentration of BMDCs. Taken all together, these results suggest that the morphological and functional interactions between enteric neurons and DCs may be involved in the pathogenesis of the colitis.
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