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Agent-Based Network Modeling Study of Immune Responses in Progression of Ulcerative Colitis
Dao-rong Wu,Hai-shan Yu,Jie-lou Liao*
Author NameAffiliationE-mail
Dao-rong Wu Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, China  
Hai-shan Yu Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, China  
Jie-lou Liao* Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, China liaojl@ustc.edu.cn 
Abstract:
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-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-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.
Key words:  Network model  Agent-based method  Immune response  Ulcerative colitis
FundProject:This work was supported by the National Natural Science Foundation of China (No.21273209).
基于主体网络建模研究溃疡性结肠炎发展过程中的免疫反应动力学
吴道荣,余海山,廖结楼*
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DOI:10.1063/1674-0068/31/cjcp1710187
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