科研之友
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摘要
Ulcerative colitis, an inflammatory bowel disease, is a chronic inflammatory disorder that results in ulcers of the colon and rectum without known etiology. Ulcerative colitis causes a huge public health care burden particularly in developed countries. Many studies suggest that ulcerative colitis results from an abnormal immune response against components of commensal microbiota in genetically susceptible individuals. However, understanding of the disease mechanisms at cellular and molecular levels remains largely elusive. In this paper, a network model is developed based on our previous study and computer simulations are performed using an agent-based network modeling to elucidate the dynamics of immune response in ulcerative colitis progression. Our modeling study identifies several important positive feedback loops as a driving force for ulcerative colitis initiation and progression. The results demonstrate that although immune response in ulcerative colitis patients is dominated by anti-inflammatory/regulatory cells such as alternatively activated macrophages and type II natural killer T cells, proinflammatory cells including classically activated macrophages, T helper 1 and T helper 17 cells, and their secreted cytokines tumor necrosis factor-alpha, interleukin-12, interleukin-23, interleukin-17 and interferon-gamma remain at certain levels (lower than those in Crohn's disease, another inflammatory bowel disease). Long-term exposure to these proinflammatory components, causes mucosal tissue damage persistently, leading to ulcerative colitis. Our simulation results are qualitatively in agreement with clinical and laboratory measurements, offering novel insight into the disease mechanisms.
- 出版日期2018-4
- 单位中国科学技术大学
