The Role of the Mesentery in Crohnʼs Disease

Abstract

Crohn's disease (CD) is a complex gastrointestinal disorder involving multiple levels of cross talk between the immunological, neural, vascular, and endocrine systems. The current dominant theory in CD is based on the unidirectional axis of dysbiosis-innate immunity-adaptive immunity-mesentery-body system. Emerging clinical evidence strongly suggests that the axis be bidirectional. The morphologic and/or functional abnormalities in the mesenteric structures likely contribute to the disease progression of CD, to a less extent the disease initiation. In addition to adipocytes, mesentery contains nerves, blood vessels, lymphatics, stromal cells, and fibroblasts. By the secretion of adipokines that have endocrine functions, the mesenteric fat tissue exerts its activity in immunomodulation mainly through response to afferent signals, neuropeptides, and functional cytokines. Mesenteric nerves are involved in the pathogenesis and prognosis of CD mainly through neuropeptides. In addition to angiogenesis observed in CD, lymphatic obstruction, remodeling, and impaired contraction maybe a cause and consequence of CD. Lymphangiogenesis and angiogenesis play a concomitant role in the progress of chronic intestinal inflammation. Finally, the interaction between neuropeptides, adipokines, and vascular and lymphatic endothelia leads to adipose tissue remodeling, which makes the mesentery an active participator, not a bystander, in the disease initiation and precipitation CD. The identification of the role of mesentery, including the structure and function of mesenteric nerves, vessels, lymphatics, and fat, in the intestinal inflammation in CD has important implications in understanding its pathogenesis and clinical management.

Lipopolysaccharides modulate intestinal epithelial permeability and inflammation in a species-specific manner

“…[2][3][4] Furthermore, peripheral inflammation can subsequently result in a high incidence of arthritis associated with the disease, issues within the cardiovascular system, and lymphatic remodeling. [5][6][7][8] CD is characterized by a chronic and transmural inflammation that can be noted along the entire length of the GI tract, from mouth to anus, but primarily occurs within the colon and small intestine. The associated inflammation can promote the development of lesions at any point along the tract effecting all layers of the intestine, producing strictures and fistulae.…”

The Role of Mesenteric Adipose Tissue in Crohn’s Disease

“…These alterations demonstrate the role of mesenteric blood vessels in chronic intestinal inflammation [38,40,41]. Changes in vascular endothelium and abnormal leukocyte recruitment were also verified in CD [42].…”

“…A l t h o u g ha d i p o s et i s s u ei sa b l et oi n c r e a s eT N F -α secretion via leptin, a hormone produced by adipocytes [56], some studies in the literature did not find high levels of TNF-α in the MAT of CD, neither higher levels of IL-1B, IL6, IL8, IL23, and NF-KB activation [21,31,38,57]. Again, on the one hand, a decrease NF-kB pathway activation (d e c re a s e dp I K B / I K Br a t i o )a n di n c re a s e dI L -1 0 expression in MAT of CD patients have been demonstrated, which suggest a possible antiinflammatory role of MAT [21,31].…”

“…In an experimental study, functional and structural alterations were observed in the mesenteric nerves of animals with colitis. Mice with colitis induced by trinitrobenzene sulfonic acid or acetic acid presented hyperexcitability of visceromotor neurons causing changes in the lower mesenteric ganglia during the intestinal inflammatory process [38,46].…”

“…A recent study showed the presence of fibrosis, inflamed perivascular, thickened lymphatic vessels, infiltration of stromal cell, perineuronal chronic inflammation, engorgement of vasa recta, and small-sized adipocytes of MAT in patients with active CD [38]. MAT is divided into avascular and vascular regions.…”