Helicobacter-induced inflammatory bowel disease in IL-10- and T cell-deficient mice

2001 ◽  
Vol 281 (3) ◽  
pp. G764-G778 ◽  
Author(s):  
Andrew Burich ◽  
Robert Hershberg ◽  
Kim Waggie ◽  
Weiping Zeng ◽  
Thea Brabb ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Bowel Disease ◽  
Wild Type ◽  
Immunodeficient Mice ◽  
Inflammatory Bowel ◽  
Rag 1

Inflammatory bowel disease (IBD) is thought to result from a dysregulated mucosal immune response to luminal microbial antigens, with T lymphocytes mediating the colonic pathology. Infection with Helicobacter spp has been reported to cause IBD in immunodeficient mice, some of which lack T lymphocytes. To further understand the role of T cells and microbial antigens in triggering IBD, we infected interleukin (IL)-10−/−, recombinase-activating gene (Rag)1−/−, T-cell receptor (TCR)-α−/−, TCR-β−/−, and wild-type mice with Helicobacter hepaticus or Helicobacter bilis and compared the histopathological IBD phenotype. IL-10−/−mice developed severe diffuse IBD with either H. bilis or H. hepaticus, whereas Rag1−/−, TCR-α−/−, TCR-β−/−, and wild-type mice showed different susceptibilities to Helicobacter spp infection. Proinflammatory cytokine mRNA expression was increased in the colons of Helicobacter-infected IL-10−/−and TCR-α−/−mice with IBD. These results confirm and extend the role of Helicobacter as a useful tool for investigating microbial-induced IBD and show the importance, but not strict dependence, of T cells in the development of bacterial-induced IBD.

scholarly journals TRAIL suppresses gut inflammation and inhibits colitogeic T-cell activation in experimental colitis via an apoptosis-independent pathway

2019 ◽  
Vol 12 (4) ◽  
pp. 980-989 ◽  
Author(s):  
I. T. Chyuan ◽  
H. F. Tsai ◽  
C. S. Wu ◽  
P. N. Hsu
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Bowel Disease ◽  
Cell Activation ◽  
Gut Inflammation ◽  
Inflammatory Bowel ◽  
Colitis Model

AbstractTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cell apoptosis by transducing apoptosis signals. Recently, accumulating evidence demonstrated that TRAIL regulates autoimmune inflammation and immune cell homeostasis in several autoimmune animal models, suggesting a novel immunoregulatory role of TRAIL in autoimmune diseases. However, the impact of TRAIL in inflammatory bowel disease is yet undefined. This study is to address the therapeutic effects and immunoregulatory role of TRAIL in autoimmune gut inflammation. We demonstrated herein that TRAIL significantly suppressed gut inflammation and reduced the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis model. Suppression of gut inflammation was not due to induction of apoptosis in colonic T cells, dendritic cells, or epithelium cells by TRAIL. In contrast, TRAIL directly inhibited activation of colitogenic T cells and development of gut inflammation in an adoptive transfer-induced colitis model. The anti-inflammatory effects of TRAIL on colitis were abolished when T cells from TRAIL receptor (TRAIL-R) knockout mice were adoptively transferred, suggesting that TRAIL regulates autoreactive colitogenic T-cell activation in the development of gut inflammation. Our results demonstrate that TRAIL effectively inhibited colonic T-cell activation and suppressed autoimmune colitis, suggesting a potential therapeutic application of TRAIL in human inflammatory bowel disease.

scholarly journals Alteration of Interleukin 4 Production Results in the Inhibition of T Helper Type 2 Cell–Dominated Inflammatory Bowel Disease in T Cell Receptor α Chain–Deficient Mice

1999 ◽  
Vol 190 (5) ◽  
pp. 607-616 ◽  
Author(s):  
Hideki Iijima ◽  
Ichiro Takahashi ◽  
Daisuke Kishi ◽  
Jin-Kyung Kim ◽  
Sunao Kawano ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Bowel Disease ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
T Helper ◽  
Inflammatory Bowel ◽  
Α Chain

T cell receptor α chain–deficient (TCR-α−/−) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4+TCR-ββ (CD4+ββ) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4+ββ T cells, we treated TCR-α−/− mice with anti–IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-α−/− mice, including those treated with mock Ab and those left untreated, spontaneously developed IBD. However, anti–IL-4 mAb–treated mice exhibited no clinical or histological signs of IBD, and their levels of mucosal and systemic Ab responses were lower than those of mock Ab–treated mice. Although TCR-α−/− mice treated with either specific or mock Ab developed CD4+ββ T cells, only those treated with anti–IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon γ–specific expression. These findings suggest that IL-4–producing Th2-type CD4+ββ T cells play a major immunopathological role in the induction of IBD in TCR-α−/− mice, a role that anti–IL-4 mAb inhibits by causing Th2-type CD4+ββ T cells to shift to the Th1 type.

scholarly journals Role of regulatory T cell in the pathogenesis of inflammatory bowel disease

2016 ◽  
Vol 22 (7) ◽  
pp. 2195-2205 ◽  
Author(s):  
Akiko Yamada ◽  
Rieko Arakaki ◽  
Masako Saito ◽  
Takaaki Tsunematsu ◽  
Yasusei Kudo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
Bowel Disease ◽  
Regulatory T Cell ◽  
Inflammatory Bowel

scholarly journals Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease

2020 ◽  
Vol 14 (12) ◽  
pp. 1724-1733
Author(s):  
R Kalla ◽  
A T Adams ◽  
N T Ventham ◽  
N A Kennedy ◽  
R White ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
Bowel Disease ◽  
Whole Blood ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Prognostic Models ◽  
Inflammatory Bowel ◽  
Treatment Escalation

Abstract Background MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. Methods In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn’s disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. Results In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20–3.27; logrank p = 1.80 × 10–3), in particular CD [HR 2.81; IQR: 1.11–3.53, p = 6.50 × 10–4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. Interpretation We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

The role of PIM kinases in human and mouse CD4+ T cell activation and inflammatory bowel disease

2012 ◽  
Vol 272 (2) ◽  
pp. 200-213 ◽  
Author(s):  
Leila J. Jackson ◽  
Jed A. Pheneger ◽  
Tracy J. Pheneger ◽  
Gregg Davis ◽  
A. Dale Wright ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
T Cell Activation ◽  
Bowel Disease ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Pim Kinases ◽  
Inflammatory Bowel ◽  
Human And Mouse

scholarly journals The Role of T cell PPAR γ in mice with experimental inflammatory bowel disease

2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Amir J Guri ◽  
Saroj K Mohapatra ◽  
William T Horne ◽  
Raquel Hontecillas ◽  
Josep Bassaganya-Riera
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
Bowel Disease ◽  
Ppar Γ ◽  
Experimental Inflammatory Bowel Disease ◽  
Inflammatory Bowel

scholarly journals Store-Operated Calcium Entry Controls Innate and Adaptive Immune Cell Function in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Marilena Letizia ◽  
Ulrike Kaufmann ◽  
Yin-Hu Wang ◽  
Lorenz Gerbeth ◽  
Annegret Sand ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
Immune Cells ◽  
Bowel Disease ◽  
Clinical Course ◽  
Lymphoid Cells ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Pharmacologic Inhibition

AbstractObjectiveInflammatory bowel disease (IBD) is characterized by dysregulated intestinal immune responses and constitutes a major clinical challenge in need of new treatment modalities to improve patient care. Store-operated Ca2+ entry (SOCE) is the predominant Ca2+ influx pathway in T cells and other immune cells, regulating many of their functional properties. It is currently unknown whether the pharmacologic blockade of SOCE represents a suitable drug-target for IBD treatment.DesignUsing mass and flow cytometry the effects of SOCE inhibition on lamina propria (LP) immune cells of patients with ulcerative colitis (UC) and Crohn’s disease (CD) were investigated. Primary organoid cultures served to study the impact of SOCE inhibition on the function, differentiation and survival of intestinal epithelial cells (IEC). T cell transfer models of colitis were applied to examine how the genetic or pharmacologic ablation of SOCE affects the clinical course of IBD in mice.ResultsWe observed that the LP of IBD patients is characterized by an enrichment of innate lymphoid cells (ILC), CD4+ and CD8+ effector- as well as T regulatory cells producing IL-17 and TNFα. The pharmacologic inhibition of SOCE attenuated the production of pathogenic cytokines including IL-2, IL-4, IL-6, IL-17, TNFα and IFNγ by human colonic T cells and ILC, reduced the production of IL-6 by B cells and the production of IFNγ by myeloid cells, without affecting the viability, differentiation and function of primary IEC. T cell-specific genetic deletion of the SOCE signaling components Orai1, Stim1 or Stim2 revealed that the magnitude of SOCE correlates with the function of T cells and intestinal inflammation in mice. Moreover, the pharmacologic inhibition of SOCE alleviated the clinical course of colitic mice.ConclusionOur data suggest that SOCE inhibition may serve as a new pharmacologic strategy for treating IBD.

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