Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction: An exploratory proposal based on basic and clinical data

Figure 2 Inside-out model of Crohn’s disease pathogenesis. A: Phase I, intracellular bacteria infect into lymphatic system with few signs of intestinal mucosal injury; B: Phase II, Pathogens infect and persist in intestinal lymphatic tissues, which causes an ‘immunological scar’ in the intestinal lymphatic system. The impaired transport function, lymphangitis, lymphadenopathy, loss of button-like junctions, bacteria translocation to mesenteric lymph nodes and Peyer’s patches, and mesenteric adipose tissue formation have been found in the pathogenesis of Crohn’s disease (CD); C: Phase III, Mucosal injury as the terminal event of CD. Lymphatic dysfunction, including impaired clearance, defective dendritic cells migration, and obstruction, provides opportunities for bacteria and their by-products flowing back to the draining lymphatic vessels and causing mucosal lesions. DC: Dendritic cells; MLN: Mesenteric lymph nodes; PPs: Peyer’s patches.