The role of lymphatics in intestinal inflammation

Abstract

The lymphatic vasculature returns filtered interstitial arterial fluid and tissue metabolites to the blood circulation. It also plays a major role in lipid absorption and immune cell trafficking. Lymphatic vascular defects have been revealed in inflammatory diseases, Crohn’s disease, obesity, cardiovascular disease, hypertension, atherosclerosis, and Alzheimer’s disease. In this review, we discuss lymphatic structure and function within the gut, such as dietary lipid absorption, the transport of antigens and immune cells to lymph nodes, peripheral tolerance, and lymphocyte migration from secondary lymphoid tissues to the lymphatics and the immune systems. We also discuss the potential roles of these lymphatics on the pathophysiology of inflammatory bowel disease and as new targets for therapeutic management.

Identification of master regulator genes controlling pathogenic CD4+ T cell fate in inflammatory bowel disease through transcriptional network analysis

“…To characterize the transcriptional profile of CD4 + T cells under gut inflammation conditions, we isolate conventional CD4 + T cells (CD4 + TCRb + GFP - ) from colonic lamina propria. Despite mesenteric lymph nodes, which drain the colonic tissue, might be considered a proper control to compare what is happening in the lamina propria 31 , we chose splenic CD4 + T cells as a control since our previous studies have shown a similar profile between T cells isolated from colonic lamina propria and mesenteric lymph nodes, but different from those isolated from the spleen upon gut inflammation 14 , 32 . Then, we performed bulk RNA sequencing on these samples, and then compared the inflamed condition with the control.…”

Pathophysiology, Diagnosis, and Management of Canine Intestinal Lymphangiectasia: A Comparative Review

“…In addition to returning fluid to the blood vasculature, lymphatics are the primary transporter of lipid and lipid-soluble substances (including lipid-soluble vitamins) from the intestine to the blood. The specific molecular methods that regulate uptake of chylomicrons into lacteals are not well understood, however it is known that this task cannot be completed through portal blood absorption [ 1 , 6 , 7 , 8 ].…”

“…Notably, lymphatic abnormalities have been increasingly recognized as contributing to the pathogenesis of IBD. Importantly, impaired lymphatic drainage due to dilation, obstruction, and dysfunction results in the accumulation of fluid and infiltrating immune cells, thus setting up chronic edema and inflammation [ 8 , 9 , 15 ]. In humans with IBD, increased lymphangiectasia, lymphadenopathy and lymphatic obstruction correlate with a poor prognosis.…”

“…In humans with Crohn’s disease, many studies describe concurrent lymphangiectasia, lymphangitis, lymphangiogenesis, and other lymphatic lesions [ 9 , 12 , 36 , 63 ]. Laboratory models suggest that normalization of lymphatic structure and function improves intestinal inflammation [ 8 , 14 , 16 , 86 , 87 ]. In one study, 61% of patients with CD not experiencing symptom relief despite various combinations of pharmaceuticals and dose escalations achieved clinical remission following institution of an exclusionary diet that was also low in fat and contained a moderate amount of soluble fiber [ 88 ].…”

Targeting lymph nodes for enhanced cancer vaccination: From nanotechnology to tissue engineering

“…Particles or molecules in blood hold the possibility to enter LNs via high endothelial venules (HEVs), but this pathway may lead to a relatively low LN-targeting efficiency since substances in blood will have many ways to go or be captured [ 12 , 13 ]. On the other hand, a LN is “protected” by a fibrous capsule that is basically not permeable, and therefore reaching into LNs generally need to enter the lymphatics which have higher permeability [ 14 ], and then arrive LNs via the afferent lymphatic vessels. Particles entering lymphatics via a cell-free passive diffusion can be classified as the “passive transport”, while particles reaching into LNs by using cells ( e.g.…”