Neurogenic Monocyte Recruitment Drives Pathogenic Enteric Nervous System Remodeling in IBD

Inflammatory bowel disease (IBD) dysregulates GI physiology including bowel movements (motility), but in many IBD patients, GI motility disorders persist in remission through a poorly understood pathological process. Here we uncover that post-inflammatory GI dysmotility (PI-GID) stems from structural ENS remodeling driven by a combination of neuronal loss and neurogenesis.

Enteric neurons respond to mucosal inflammation by upregulating CCL2 expression and facilitating the recruitment of CCR2+ monocytes into the neural myenteric plexus of the intestinal muscle followed by the expansion of monocyte-derived macrophages, their migration into the myenteric ganglia and phagocytosis of neurons. However, excessive recruitment of monocytes promotes disproportionate ENS remodeling and PI-GID. Expansion of immune cells in the tissue also promotes tissue hypoxia.