Role of the lymphatic system in the pathogenesis of Crohnʼs disease

Abstract

Improved knowledge and appreciation of the roles that the lymphatic system plays in immune cell trafficking, infection, fat transport, distribution and metabolism and, of course, edema resolution is necessary to better understand the pathogenesis of chronic inflammatory conditions such as Crohn's disease and may provide the basis for new therapeutic strategies.

Anatomy and roles of lymphatics in inflammatory diseases

“…Impaired mesenteric lymphatic function results in adipose deposition encircling the inflamed segments of the gut, consistent with impaired mesenteric lymphatic pumping limiting lipid conductance and fat wrapping in IBD. 115,120 Although increased density of lymphatics is a characteristic of experimental and clinical IBD, lymphatic vessel dilation and edema formation in IBD could also be a consequence of impaired contractile function of the intestinal lymphatics. 121,122 In rat and guinea pig models of intestinal inflammation, indeed, the contractile capacity within isolated collecting mesenteric lymphatics is compromised, and this effect correlates with lymphatic dysfunction, lymphatic vessel dilation and mucosal inflammation.…”

“…[112][113][114] Lymphoid aggregates, inflammatory granulomas and "fat wrapping" (fat creeping up onto the bowel) suggest a general failure of lymphatics to adequately transport inflammatory cells and lipids. 115 In Crohn's disease, compromised lymphatic pumping reduces immune cell trafficking from tissues to local LN, which results in immune cell accumulation in tissues, delaying but possibly intensifying the nodal immune response against pathogens. 116 Obstructive lymphoid aggregates (immune cell clusters), which contain macrophages and lymphocytes, were among the first histopathological features described in Crohn's disease, and can provoke and also result from poor lymphatic drainage, which reflects impaired lymphatic conduction and pumping.…”

Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease

“…Indeed, lymphatic dysfunction has been long discussed, although often overlooked, in Crohn disease (CD). 4,5 In particular, the sites where lymphatic dysfunction may be most relevant are scarcely studies in inflammatory bowel disease (IBD) models. That is, most analysis is performed in the intestinal wall, where lymphatic capillaries take up immune cells and solutes from the interstitium.…”

Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis

“…Perturbation of this tightly regulated process has been reported to exacerbate inflammation in chronic inflammatory disorders, including rheumatoid arthritis, experimental arthritis, psoriasis, and Crohn disease. [3][4][5][20][21][22] TNF is involved in the pathogenesis of all of these disorders. The current findings showing that TNF inhibits key LEC functions, including tube formation, migratory capacity, and lymphatic sprouting, confirm previous reports that demonstrate the overt anti-lymphatic effects of TNF.…”