Animal Models of Inflammatory Disease Provides Pathogenic Insight
Inflammatory bowel diseases (IBD) are autoimmune conditions in which the immune system attacks regions of the digestive system. Crohn’s disease (CD) and ulcerative colitis (UC) are the two most common forms of IBD, differing in nature and location of inflammation within the digestive system. Although there are notable differences between CD and UC – which can both be further subphenotyped within their own specific conditions – they do appear to share some common genetic factors, based on the incidence of both diseases within the same ethnic groups. Although there are clearly contributing environmental factors in both CD and UC that add to the complexity of studying the many etiological factors, animal models of inflammatory disease have been an important source of insight into intestinal microbiota in IBD and immunologic dysregulation factors.
Mouse models of colitis have demonstrated the importance of mucosal homeostasis within the intestinal lining, as the disruption in mucosal function leads to spontaneous colitis. Immune regulation within the intestinal walls relies on mucosal homeostasis. Cells that comprise the mucosal membrane lining the intestines – which is comprised of the epithelium and lamina propria – include goblet and paneth cells. Along with secretory immunoglobulin A, these cells secrete mucus and anti-microbial peptides that support the barrier’s immunological function. Th1 and Th17 cells, which drive inflammation, are triggered and regulated by cytokines IL-23, TNF-a, and TGF-b, or suppressive TGF-b and IL-10 cytokines. Activation or ablation of certain factors – including transcription factor NF-KB – have been shown to improve or hinder resistance to disease.
Identifying the factors underlying immunologic dysregulation that contribute to IBD symptoms in animal models helps researchers identify responsible genes and causative mutations within those genes. In addition to in-depth mouse model analyses, genome-wide association studies among IBD patients has been underway in the last several years, to help identify a growing number of CD genes. Progressive findings on all fronts help bolster investigations all around and improve animal models of inflammatory disease so that they are further modeled based on human genetics.
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Categories: Inflammatory diseases