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

Katsandegwaza, Brunette; Horsnell, William; Smith, Katherine A.

doi:10.3390/ijms23169344

Cited by 76 publications

(43 citation statements)

References 156 publications

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“…Colon inflammation was scored following a published scoring system for induced colitis 18 , with modifications (Suppl. Table S2 ) to take into account the spontaneous nature of colitis in the present model and the histological differences, particularly with regard to tissue swelling observed in classical experimental models 19 . As can be seen from Fig.…”

Section: Resultsmentioning

confidence: 99%

Colitis in a transgenic mouse model of autoimmune uveitis may be induced by neoantigen presentation in the bowel

Mölzer

Liu

Muckersie

et al. 2023

Sci Rep

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Undifferentiated uveitis (intraocular inflammation, IOI) is an idiopathic sight-threatening, presumed autoimmune disease, accountable for ~ 10% of all blindness in the developed world. We have investigated the association of uveitis with inflammatory bowel disease (IBD) using a mouse model of spontaneous experimental autoimmune uveoretinitis (EAU). Mice expressing the transgene (Tg) hen egg lysozyme (HEL) in the retina crossed with 3A9 mice expressing a transgenic HEL-specific TCR spontaneously develop uveoretinitis at post-partum day (P)20/21. Double transgenic (dTg TCR/HEL) mice also spontaneously develop clinical signs of colitis at ~ P30 with diarrhoea, bowel shortening, oedema and lamina propria (LP) inflammatory cell infiltration. Single (s)Tg TCR (3A9) mice also show increased histological LP cell infiltration but no bowel shortening and diarrhoea. dTg TCR/HEL mice are profoundly lymphopenic at weaning. In addition, dTg TCR/HEL mice contain myeloid cells which express MHC Class II-HEL peptide complexes (MHCII-HEL), not only in the inflamed retina but also in the colon and have the potential for antigen presentation. In this model the lymphopenia and reduction in the absolute Treg numbers in dTg TCR/HEL mice is sufficient to initiate eye disease. We suggest that cell-associated antigen released from the inflamed eye can activate colonic HEL-specific T cells which, in a microbial micro-environment, not only cause colitis but feedback to amplify IOI.

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Section: Resultsmentioning

confidence: 99%

Colitis in a transgenic mouse model of autoimmune uveitis may be induced by neoantigen presentation in the bowel

Mölzer

Liu

Muckersie

et al. 2023

Sci Rep

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“…The common preclinical murine models of UC include the DSS-induced colitis model, trinitrobenzene sulfonic acid (TNBS)-induced colitis model and IL-10-deficient mouse model ( 20 ). Various studies have demonstrated that IL-10 suppresses inflammation in colitis by regulating innate and adaptive immune responses, such as promoting the expansion of Treg cells to suppress the immune response mediated by Th17 cells, which indicates that IL-10-deficient mice were not suitable for the present study ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Polysaccharide from Atractylodes macrocephala Koidz. ameliorates DSS-induced colitis in mice by regulating the Th17/Treg cell balance

et al. 2022

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Atractylodes macrocephala Koidz. is one of the most frequently used traditional Chinese medicines for the treatment of ulcerative colitis (UC). The beneficial effect of polysaccharide from Atractylodes macrocephala Koidz. (PAMK) on UC has been reported, while the underlying mechanism and target remain unclear. In this study, we systematically investigated the therapeutic effect and the underlying mechanism of PAMK in UC based on a mouse model of dextran sodium sulfate (DSS)-induced colitis. PAMK treatment (100 mg/kg, 200 mg/kg and 400 mg/kg) significantly ameliorated DSS-induced colitis, manifested as a reduction in weight loss, disease activity index (DAI), colon shortening, spleen index and histological score. Moreover, PAMK treatment inhibited inflammation and improved the integrity of the intestinal barrier in colitis mice. Mechanistically, microarray analysis determined the critical role of the immunoregulatory effect of PAMK in alleviating UC. Flow cytometry analysis further demonstrated that PAMK treatment regulated the balance between T helper (Th) 17 and regulatory T (Treg) cells in the mesenteric lymph nodes (MLN) and spleen in mice with colitis. In addition, PAMK treatment downregulated the expression of IL-6 and suppressed the phosphorylation of STAT3. Together, these data revealed that PAMK treatment alleviated DSS-induced colitis by regulating the Th17/Treg cell balance, which may be dependent on the inhibition of the IL-6/STAT3 signaling pathway. Our study is the first to elucidate that the underlying mechanism by which PAMK treatment alleviates DSS-induced colitis is associated with an improved the Th17/Treg cell balance. Collectively, the study provides evidence for the potential of PAMK to treat UC.

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“…Despite of few studies of MDSCs in IBD patients, a number of studies employed murine colitis models to explore the functional roles of MDSCs. Dextran sulfate sodium (DSS)-induced, 4,6-trinitrobenzene sulfonic acid (TNBS)-induced, T cell transfer-induced or genetic defects-induced spontaneous murine colitis models were established to mimic the pathology of IBD ( 50 ). Murine MDSCs were identified as CD11b + Gr-1 + cells in most studies.…”

Section: The Dual Role Of Mdscs In the Development Of Ibdmentioning

confidence: 99%

The paradoxical role of MDSCs in inflammatory bowel diseases: From bench to bedside

Zhao

Gong²,

Song³

et al. 2022

Front. Immunol.

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Myeloid-derived suppressor cells (MDSCs) are a group of bone marrow derived heterogeneous cells, which is known for their immunosuppressive functions especially in tumors. Recently, MDSCs have receiving increasing attention in pathological conditions like infection, inflammation and autoimmune diseases. Inflammatory bowel diseases (IBD) are a series of immune-dysfunctional autoimmune diseases characterized by relapsing intestinal inflammation. The role of MDSCs in IBD remains controversial. Although most studies in vitro demonstrated its anti-inflammatory effects by inhibiting the proliferation and function of T cells, it was reported that MDSCs failed to relieve inflammation but even promoted inflammatory responses in experimental IBD. Here we summarize recent insights into the role of MDSCs in the development of IBD and the potential of MDSCs-targeted therapy.

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

Cited by 76 publications

References 156 publications

Colitis in a transgenic mouse model of autoimmune uveitis may be induced by neoantigen presentation in the bowel

Colitis in a transgenic mouse model of autoimmune uveitis may be induced by neoantigen presentation in the bowel

Polysaccharide from Atractylodes macrocephala Koidz. ameliorates DSS-induced colitis in mice by regulating the Th17/Treg cell balance

The paradoxical role of MDSCs in inflammatory bowel diseases: From bench to bedside

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