Aronia Berry Supplementation Mitigates Inflammation in T Cell Transfer-Induced Colitis by Decreasing Oxidative Stress

Oxidative stress is involved in the pathogenesis and progression of inflammatory bowel disease. Consumption of aronia berry inhibits T cell transfer colitis, but the antioxidant mechanisms pertinent to immune function are unclear. We hypothesized that aronia berry consumption could inhibit inflammation by modulating the antioxidant function of immunocytes and gastrointestinal tissues. Colitis was induced in recombinase activating gene-1 deficient (Rag1-/-) mice injected with syngeneic CD4+CD62L+ naïve T cells. Concurrent with transfer, mice consumed either 4.5% w/w aronia berry-supplemented or a control diet for five weeks. Aronia berry inhibited intestinal inflammation evidenced by lower colon weight/length ratios, 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake, mRNA expressions of tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) in the colon. Aronia berry also suppressed systemic inflammation evidenced by lower FDG uptake in the spleen, liver, and lung. Colitis induced increased colon malondialdehyde (MDA), decreased colon glutathione peroxidase (GPx) activity, reduced glutathione (rGSH) level, and suppressed expression of antioxidant enzymes in the colon and mesenteric lymph node (MLN). Aronia berry upregulated expression of antioxidant enzymes, prevented colitis-associated depletion of rGSH, and maintained GPx activity. Moreover, aronia berry modulated mitochondria-specific antioxidant activity and decreased splenic mitochondrial H2O2 production in colitic mice. Thus, aronia berry consumption inhibits oxidative stress in the colon during T cell transfer colitis because of its multifaceted antioxidant function in both the cytosol and mitochondria of immunocytes.

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P032 MiR-511 deficiency aggravates T cell transfer colitis in mice

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.161 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S147-S147

Author(s):

S Rahman ◽

A Elfiky ◽

P H P van Hamersveld ◽

C Verseijden ◽

O Welting ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Intestinal Inflammation ◽

Activity Index ◽

Disease Activity Index ◽

Cell Populations ◽

Spleen Weight ◽

Cell Transfer ◽

Rag 1 ◽

T Cell Transfer

Abstract Background MiR-511 is embedded in intron region 5 of the CD206/MRC1 gene, expressed by macrophage and dendritic cell populations. In this study, we aimed to investigate the effect of MiR-511 deficiency on intestinal inflammation in a murine T cell transfer colitis model. Methods A double MiR-511- and Rag-1 (knockout) KO mouse was generated and a T cell transfer colitis was induced by intraperitoneal injection of naïve T cells from donor WT mice. Since these mice lack mature T and B cells, first signs of inflammation appeared at week 3 after T cell injection. An endoscopy score was obtained to determine inflammation at week 3 and 5, respectively. The experiment was terminated at week 5 and severity of inflammation was assessed on the basis of weight loss, colon weight/length ratio, histology score, spleen weight and disease activity index. In addition, flow cytometry was performed for analysing immune cell populations (monocyte, macrophages, dendritic cells, neutrophils) in the colons of both control and colitis groups and T cells in the spleens of colitis group, respectively. Results Following the induction of T cell transfer colitis, colon weight/length ratio, spleen weight and endoscopic score were significantly increased in the double KO mice compared to Rag-1 KO control mice. A higher histology score and disease activity index in the double KO with no change in weight loss compared to Rag-1 KO control mice was observed. A significant increase in monocyte population in the colons of double KO was seen and increased numbers of monocytes was also observed in the double KO control group with no inflammation. Also, a higher influx of T cells in the double KO mice with a significant increase in Foxp3 and IL4 population was observed in the group with colitis. Conclusion MiR-511 deficiency aggravates intestinal inflammation compared to Rag-1 KO control mice. Also, a higher presence of monocyte as well as T cell populations were observed in these mice. Together these data show that MiR-511 is involved in the regulation of intestinal health. Future research will focus on underlying mechanisms.

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T Cell Transfer Model of Colitis: A Great Tool to Assess the Contribution of T Cells in Chronic Intestinal Inflammation

Methods in Molecular Biology - Leucocytes ◽

10.1007/978-1-61779-527-5_19 ◽

2011 ◽

pp. 261-275 ◽

Cited By ~ 22

Author(s):

Rajaraman Eri ◽

Michael A. McGuckin ◽

Robert Wadley

Keyword(s):

T Cells ◽

T Cell ◽

Intestinal Inflammation ◽

Transfer Model ◽

Cell Transfer ◽

T Cell Transfer ◽

Chronic Intestinal Inflammation

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Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00071.2003 ◽

2003 ◽

Vol 285 (4) ◽

pp. G754-G760 ◽

Cited By ~ 10

Author(s):

N. Dan ◽

T. Kanai ◽

T. Totsuka ◽

R. Iiyama ◽

M. Yamazaki ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lamina Propria ◽

Fas Ligand ◽

Intestinal Inflammation ◽

Therapeutic Effects ◽

Cell Transfer ◽

Chronic Colitis ◽

Wasting Disease ◽

T Cell Transfer

Fas/Fas ligand (FasL) interaction has been implicated in the pathogenesis of various diseases. To clarify the involvement of Fas/FasL in the pathogenesis of intestinal inflammation, we investigated the preventive and therapeutic effects of neutralizing anti-FasL monoclonal antibody (MAb) on the development of chronic colitis induced by adaptive transfer of CD4+CD45RBhigh T cells to SCID mice. Administration of anti-FasL MAb from 1 day after T cell transfer (prevention study) resulted in a significant improvement of clinical manifestations such as wasting and diarrhea. However, histological examination showed that mucosal inflammation in the colon, such as infiltration of T cells and macrophages, was not improved by the anti-FasL MAb treatment. In vitro studies showed that anti-FasL MAb did not inhibit IFN-γ production by anti-CD3/CD28-stimulated lamina propria CD4+ T cells but suppressed TNF-α and IL-1β production by lamina propria mononuclear cells. Therapeutic administration of anti-FasL MAb from 3 wk after T cell transfer also improved ongoing wasting disease but not intestinal inflammation. These results suggest that the Fas/FasL interaction plays a critical role in regulating systemic wasting disease but not local intestinal inflammation.

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Commensal epitopes drive differentiation of colonic Tregs

Science Advances ◽

10.1126/sciadv.aaz3186 ◽

2020 ◽

Vol 6 (16) ◽

pp. eaaz3186 ◽

Cited By ~ 7

Author(s):

Michal P. Kuczma ◽

Edyta A. Szurek ◽

Anna Cebula ◽

Benoit Chassaing ◽

Yu-Jin Jung ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Receptors ◽

Intestinal Inflammation ◽

Transfer Model ◽

Cell Transfer ◽

Wasting Disease ◽

New Approach ◽

Lymphocyte Responses ◽

T Cell Transfer

The gut microbiome is the largest source of intrinsic non–self-antigens that are continuously sensed by the immune system but typically do not elicit lymphocyte responses. CD4+ T cells are critical to sustain uninterrupted tolerance to microbial antigens and to prevent intestinal inflammation. However, clinical interventions targeting commensal bacteria–specific CD4+ T cells are rare, because only a very limited number of commensal-derived epitopes have been identified. Here, we used a new approach to study epitopes and identify T cell receptors expressed by CD4+Foxp3+ (Treg) cells specific for commensal-derived antigens. Using this approach, we found that antigens from Akkermansia muciniphila reprogram naïve CD4+ T cells to the Treg lineage, expand preexisting microbe specific Tregs, and limit wasting disease in the CD4+ T cell transfer model of colitis. These data suggest that the administration of specific commensal epitopes may help to widen the repertoire of specific Tregs that control intestinal inflammation.

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Nematode Asparaginyl-tRNA Synthetase Resolves Intestinal Inflammation in Mice with T-Cell Transfer Colitis

Clinical and Vaccine Immunology ◽

10.1128/cvi.00594-12 ◽

2012 ◽

Vol 20 (2) ◽

pp. 276-281 ◽

Cited By ~ 18

Author(s):

Michael A. Kron ◽

Ahmed Metwali ◽

Sanja Vodanovic-Jankovic ◽

David Elliott

Keyword(s):

T Cell ◽

Cellular Response ◽

Intestinal Inflammation ◽

Trna Synthetase ◽

Therapeutic Effects ◽

Cell Transfer ◽

Content Type ◽

Anti Inflammatory ◽

T Cell Transfer

ABSTRACTThe therapeutic effects of a controlled parasitic nematode infection on the course of inflammatory bowel disease (IBD) have been demonstrated in both animal and human models. However, the inability of individual well-characterized nematode proteins to recreate these beneficial effects has limited the application of component immunotherapy to human disease. The nematodes that cause chronic human lymphatic filariasis,Brugia malayiandWuchereria bancrofti, are among the parasites that induce immune suppression. Filarial lymphatic pathology has been shown to involve NF-κB pathway-dependent production of vascular endothelial growth factor (VEGF), and stimulation of VEGF expression has also been reported by interleukin 8 (IL-8) via NF-κB pathways. Previously, we have shown that the filarial asparaginyl-tRNA synthetase (rBmAsnRS) interacts with IL-8 receptors using a combination of extracellular loops that differ from those bound by IL-8. To test the hypothesis that rBmAsnRS might induce an anti-inflammatory effectin vivo, we studied the effects of rBmAsnRS in an established murine colitis model using T-cell transfer mice. T-cell transfer colitis mice treated intraperitoneally with 100 μg of rBmAsnRS four times over 2 weeks showed resolution of cellular infiltration in the colonic mucosa, along with induction of a CD8+cellular response. In addition, rBmAsnRS induced a rise in IL-10 production from CD3+and lipopolysaccharide (LPS)- and cytosine phosphate guanosine (CPG)-stimulated splenic cells. In summary, this work demonstrates a novel anti-inflammatory nematode protein, supports the hygiene hypothesis, and supports continued refinement of alternative immunotherapies for treatment of IBD.

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T cell transfer model of chronic colitis: concepts, considerations, and tricks of the trade

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90462.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. G135-G146 ◽

Cited By ~ 238

Author(s):

Dmitry V. Ostanin ◽

Jianxiong Bao ◽

Iurii Koboziev ◽

Laura Gray ◽

Sherry A. Robinson-Jackson ◽

...

Keyword(s):

T Cell ◽

Intestinal Inflammation ◽

Transfer Model ◽

Cell Transfer ◽

Chronic Colitis ◽

Immunological Mechanisms ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

T Cell Transfer ◽

Detailed Protocol

The inflammatory bowel diseases (Crohn's disease; ulcerative colitis) are idiopathic chronic inflammatory disorders of the intestine and/or colon. A major advancement in our understanding of the pathogenesis of these diseases has been the development of mouse models of chronic gut inflammation. One model that has been instrumental in delineating the immunological mechanisms responsible for the induction as well as regulation of intestinal inflammation is the T cell transfer model of chronic colitis. This paper presents a detailed protocol describing the methods used to induce chronic colitis in mice. Special attention is given to the immunological concepts that explain disease pathogenesis in this model, considerations and potential pitfalls in using this model, and finally different “tricks” that we have learned over the past 12 years that have allowed us to develop a more simplified version of this model of experimental IBD.

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