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 p...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 cornrnensal rnicrobiota 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 perforrned 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-inflarnrnatory/regulatory cells such as alternatively activated rnacrophages and type II natural killer T cells, proinflarnrnatory cells including classically activated rnacrophages, T helper 1 and T helper 17 cells, and their secreted cytokines tumor necrosis factor-α, interleukin-12, interleukin-23, interleukin-17 and interferon-γ remain at certain levels （lower than those in Crohn＇s disease, another inflammatory bowel disease）. Long-terrn exposure to these proinflarnrnatory components, causes rnucosal 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.展开更多
基金supported by the National Natural Science Foundation of China (No.21273209)
文摘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 cornrnensal rnicrobiota 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 perforrned 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-inflarnrnatory/regulatory cells such as alternatively activated rnacrophages and type II natural killer T cells, proinflarnrnatory cells including classically activated rnacrophages, T helper 1 and T helper 17 cells, and their secreted cytokines tumor necrosis factor-α, interleukin-12, interleukin-23, interleukin-17 and interferon-γ remain at certain levels （lower than those in Crohn＇s disease, another inflammatory bowel disease）. Long-terrn exposure to these proinflarnrnatory components, causes rnucosal 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.
