PRJNA552657
RNA-Seq of human sorted colonic macrophages from Hirschsprung's disease patients
Hirschsprung's disease (HD) is a congenital intestinal motility disorder defined by the absence of enteric ganglia cells (aganglionose) in the distal colon and characterized by bowel obstruction and the formation of a megacolon. Although, routinely treated by surgical removal of aganglionic segments the most life-threatening complication is the development of HD-associated enterocolitis with still unknown pathogenesis. Due to the lack of enteric ganglia cells HD patients show extramural innervation of acetylcholine-secreting (cholinergic) nerve fibers. Cholinergic signals have been reported to control excessive inflammatory immune responses, however, the impact on the colonic microbiom and enterocolitis manifestation in HD patients is unknown. We grouped HD patients according to their degree of mucosal cholinergic innervation in the distal colon into fiber-high and fiber-low patients. Colonic mucosal macrophages from fiber-high and fiber-low as well as muscularis macrophages from HD patients were FACS-sorted as viable CD45+HLA-DR+CD64+ cells and RNA-Seq performed. Blood-derived in vitro differentiated M1 and M2 macrophages from healthy adult donor were included as controls. These data will clarify how the presence of cholinergic neurons affect the phenotype of colonic macrophages.