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.
Article first published online 10 May 2016
*Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China; and
†Center for Inflammatory Bowel Disease, Digestive Disease Institute, The Cleveland Clinic Foundation, Cleveland, Ohio.
Reprints: Bo Shen, MD, Center for Inflammatory Bowel Disease, Desk A31, Digestive Disease Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (e-mail: firstname.lastname@example.org).
B. Shen is supported by the Ed and Joey Story Endowed Chair. W. Zhu is supported by National Science Foundation of China (81570500).
The authors have no conflicts of interest to disclose.
Received January 23, 2016
Accepted February 11, 2016