Colonic folds as a unit for lymphatic drainage and immune surveillance supporting large intestinal outflow 3839

Abstract Description The colon is characterized by histological undulations and posited to play a role in fecal formation through water absorption. While human colons exhibit haustral folds along with less pronounced intrahaustral folds, murine colons are devoid of these characteristics yet demonstrate a consistent pattern of luminal folds, particularly within the proximal region. Our advanced intravital and three-dimensional imaging techniques applied across murine and human tissues have revealed a novel function of these folds: operating for managing interstitial fluid, facilitated by a specialized lymphatic network anchored into the folds. These folds are crucial to colonic lymphatic drainage, functioning as conduits for fluid outflow and immune surveillance. The presence of lymphoid follicles and phagocytic macrophages within this system reflects an advanced role in immune surveillance, in contrast to the uniform lymphatic flow observed in the small intestine. In mice, colitis appears to compromise the structural integrity of these folds, resulting in the propagation of inflammation from distal to proximal regions, which parallels patterns seen in human ulcerative colitis, suggesting that the integrity of colonic folds may be vital to understanding the progression of IBD. In conclusion, our research posits the colonic folds as essential components in fluid dynamics and immune regulation, yielding new insights into the pathogenesis of IBD and potential therapeutic strategies. Funding Sources NIH DP1DK109668 NIH R01AI168044 NIH U01AI163064 Crohn’s & Colitis Foundation Career Developmental Award #938100 Medical Research Council Clinical Research Training Fellowship Society for Mucosal Immunology Technique-Sharing Grant Topic Categories Mucosal and Regional Immunology (MUC)