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Review
. 2022 Aug 19;23(16):9344.
doi: 10.3390/ijms23169344.

Inflammatory Bowel Disease: A Review of Pre-Clinical Murine Models of Human Disease

Brunette Katsandegwaza  1 , William Horsnell  2 , Katherine Smith  3
Affiliations
Review

Inflammatory Bowel Disease: A Review of Pre-Clinical Murine Models of Human Disease

Brunette Katsandegwaza et al. Int J Mol Sci. .

Abstract

Crohn's disease (CD) and ulcerative colitis (UC) are both highly inflammatory diseases of the gastrointestinal tract, collectively known as inflammatory bowel disease (IBD). Although the cause of IBD is still unclear, several experimental IBD murine models have enabled researchers to make great inroads into understanding human IBD pathology. Here, we discuss the current pre-clinical experimental murine models for human IBD, including the chemical-induced trinitrobenzene sulfonic acid (TNBS) model, oxazolone and dextran sulphate sodium (DSS) models, the gene-deficient I-kappa-B kinase gamma (Iκκ-γ) and interleukin(IL)-10 models, and the CD4+ T-cell transfer model. We offer a comprehensive review of how these models have been used to dissect the etiopathogenesis of disease, alongside their limitations. Furthermore, the way in which this knowledge has led to the translation of experimental findings into novel clinical therapeutics is also discussed.

Keywords: Crohn’s disease; inflammatory bowel disease; murine models; therapeutics; ulcerative colitis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immune response during oxazolone colitis. Oxazolone administration results in the production of IL-25, activation of ILC2, and production of IL-13, activating CD4+ T cell responses and amplifying type-2 cytokine production. Oxazolone administration also results in the expansion of T cells with surrogate markers of NKT cell function and IL-13 production by populations of CD1-restricted NKT cells. The resulting chronic inflammatory responses result in goblet cell depletion, increased intestinal permeability, and increased adhesion of commensal intestinal microbiota to the epithelium. Key: inflamed epithelial cells (Infl.EC), healthy epithelial cells (HEC), damaged epithelial cell (dam.EC). Created with BioRender.com, accessed on 18 August 2022.
Figure 2
Figure 2
Immune response to DSS administration. DSS administration results in epithelial release of IL-1β, activation of ILC3, and release of IL-23. IL-23 release results in the influx of neutrophils and CD4+ T cells, which further respond through enhanced IL-17 signalling. The resulting chronic inflammatory responses result in goblet cell depletion, increased intestinal permeability, and increased adhesion of commensal intestinal microbiota to the epithelium. Key: Inflamed epithelial cells (Infl.EC), healthy epithelial cells (HEC), damaged epithelial cell (dam.EC), macrophages (MΦ), neutrophils (NΦ). Created with BioRender.com, accessed on 18 August 2022.
Figure 3
Figure 3
CD45RBhiCD4+ T cell adoptive transfer scheme. Created with BioRender.com, accessed on 18 August 2022.
See this image and copyright information in PMC

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