Role of mesenteric component in Crohn’s disease: A friend or foe?

Abstract

Crohn’s disease (CD) is a complex and relapsing gastrointestinal disease with mesenteric alterations. The mesenteric neural, vascular, and endocrine systems actively take part in the gut dysbiosis-adaptive immunity-mesentery-body axis, and this axis has been proven to be bidirectional. The abnormalities of morphology and function of the mesenteric component are associated with intestinal inflammation and disease progress of CD via responses to afferent signals, neuropeptides, lymphatic drainage, adipokines, and functional cytokines. The hypertrophy of mesenteric adipose tissue plays important roles in the pathogenesis of CD by secreting large amounts of adipokines and representing a rich source of proinflammatory or profibrotic cytokines. The vascular alteration, including angiogenesis and lymphangiogenesis, is concomitant in the disease course of CD. Of note, the enlarged and obstructed lymphatic vessels, which have been described in CD patients, are likely related to the early onset submucosa edema and being a cause of CD. The function of mesenteric lymphatics is influenced by endocrine of mesenteric nerves and adipocytes. Meanwhile, the structure of the mesenteric lymphatic vessels in hypertrophic mesenteric adipose tissue is mispatterned and ruptured, which can lead to lymph leakage. Leaky lymph factors can in turn stimulate adipose tissue to proliferate and effectively elicit an immune response. The identification of the role of mesentery and the crosstalk between mesenteric tissues in intestinal inflammation may shed light on understanding the underlying mechanism of CD and help explore new therapeutic targets.

Keywords: Crohn’s disease; Mesenteric nerves; Angiogenesis; Lymphatic drainage; Mesenteric adipose tissue

Core Tip: Crohn’s disease (CD) is a complex autoimmune disease with increasing incidence worldwide, especially in Asian countries in recent years. There has been excellent progress in understanding the role of the mesentery in the pathogenesis and disease progress of CD. The crosstalk between components and intestinal inflammation has aroused many researchers’ interests. Herein, we will discuss the basic function and the alteration under inflammatory state of mesenteric nerves, blood vessels, lymphatics, and fat mass. Existing therapeutic strategies associated with mesentery components will also be summarized.