Lymphatic vessels and lymphangiogenesis in inflammatory bowel disease

Abstract

Anomalies in the lymphatic vasculature were identified in the initial descriptions of Crohn's disease on surgical specimens that had not been subjected to different drug treatments. However, it is unclear whether these morphological anomalies were early events, possibly primary, or whether these alterations were secondary to chronic inflammation. First, we mapped the lymphatic vasculature in Crohn's disease and ulcerative colitis. We therefore showed the growth of lymphatic vessels (lymphangiogenesis) in different segments of intestine, not only in inflammatory zones but also in areas devoid of inflammatory infiltrate and this feature was observed both in Crohn's disease and ulcerative colitis. We revealed that significant remodeling of lymphatic vasculature precedes the appearance of histological lesions. The mechanism causing the proliferation of lymphatic vessels in healthy zone remains poorly understood because no growth factors generally recognized as responsible for lymphangiogenesis have been found in these areas. We further found that in Crohn's disease, the degree of lymphangiogenesis in non-inflamed sections is highly variable from one patient to another. In a second step, we investigated whether this lymphangiogenesis was a sign of an early lymphatic dysfunction or if, on the contrary, it was an appropriate and adequate response found in some individuals. Using postoperative recurrence model in Crohn's disease, we showed that early lymphan-giogenesis decreased the recurrence in ileal disease. Thus, patients with low lymphatic density in non-inflamed ileal resection margin tend to have recurrence on neo terminal ileum more severely than those with high lymphatic density. It is therefore likely that in the "gut wall", lymphatic function is not initially affected. However, it appears that early alterations of lymphatics exist in the mesentery and it will be important in future works to study in parallel lymphatic alterations in the "gut wall" and in the mesentery.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201