OBSTRUCTED LYMPHATIC TRANSPORT AND LEAKAGE DRIVEN BY MESENTERIC TERTIARY LYMPHOID ORGANS IS A FEATURE OF CROHN’S DISEASE MOUSE MODEL

Abstract

Pioneer reports of Crohn’s disease (CD) suggested that impaired lymphatic flow might drive its pathogenesis but remains unsettled. Nodules of tertiary lymphoid organs (TLO) are found in association with collecting lymphatic vessels (CLVs) of the mesentery that normally conducts lymph outflow from the intestine. Whether TLOs affect lymph transport is unknown. In the TNFΔARE mouse model of Crohn’s-like ileitis, TLOs are found in valves regions. Using lymphatic reporters and photoconversion to study cell trafficking from the intestine, our findings indicated that TLOs halts immune cells traveling from the inflamed ileum to the lymph node, effectively trapping DCs, B, and T cells, and impacting the development of microbe tolerogenic regulatory T cells.