Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

Chen, Mei Lan; Sundrud, Mark S.

doi:10.1097/mib.0000000000000714

Cited by 135 publications

(118 citation statements)

References 171 publications

(212 reference statements)

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“…Aer DSS withdrawal, the pro-inammatory cytokine levels kept increasing, although at slower rates, and reached maximum levels on day 11 (TNF-a, IL-6) or day 14 (IL-1b), while the levels of both anti-inammatory cytokines (IL-4 and IL-10) were signi-cantly decreased, which on day 14 was yet much higher than the basal levels. The pattern of cytokines supports the acute selflimited character of ulcerative colitis, 34 however, the everincreasing pro-inammatory cytokines observed in DSStreated rats were different from those reported in the DSSinduced mice colitis model in which both the anti-(IL-10 and IL-12) and the pro-inammatory cytokines followed bi-phasic changes: increase with DSS stimulation and decrease aer DSS withdrawal.…”

Section: Mce Attenuated the Inammation In Rats With Colitiscontrasting

confidence: 43%

“…34 These ndings support the DSS-induced rat colitis model is suitable for studying human UC. The extract of Mori Cortex could alleviate the colitis symptoms.…”

mentioning

confidence: 61%

“…34 In the acute experimental colitis rat model induced by DSS, both pro-(TNF-a, IL-1b, IL-6) and anti-inammatory (IL-4 and IL-10) cytokines were signicantly increased aer DSS stimulation and showed a time-dependent manner (Fig. 2).…”

Section: Mce Attenuated the Inammation In Rats With Colitismentioning

confidence: 99%

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Mori Cortex regulates P-glycoprotein in Caco-2 cells and colons from rats with experimental colitis via direct and gut microbiota-mediated mechanisms

et al. 2017

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ac P-Glycoprotein dysregulation and microbial imbalance have been implicated in inflammatory bowel diseases. Here we found that oral dosing of Mori Cortex, the root bark of Morus alba L. markedly alleviated inflammatory responses, reinstated microbial balance, and enhanced P-glycoprotein (P-gp) expression in rat colitis (UC) induced by oral administration of dextran sulfate sodium. The effects of Mori Cortex extract (MCE) on colon P-gp were examined using Caco-2 cells which revealed a timedependent regulatory profile. The distinct effects on P-gp by individual main components may account for the direct biphasic effects of MCE. The involvement of gut microbiota in P-gp regulation by MCE was assessed by incubating the culture supernatant (CS) of fecal bacteria from normal, UC or MCE pretreated rats with Caco-2 cells. Interestingly, compared to normal CS, UC CS but not MCE CS diminished P-gp expression in Caco-2 cells, and this down-regulation could be reversed by pretreatment of Caco-2 cells with MCE. Moreover, MCE CS treated Caco-2 cells generated proinflammatory IL-1b and IL-8 comparable to that of the normal group and lower than the UC group, whereas, the anti-inflammatory IL-10 stimulated by MCE CS was significantly higher than the UC CS. In conclusion, MCE alleviated colitis-like symptoms and enhanced the intestinal epithelial integrity (P-gp up-regulation) in experimental colitis. The mechanisms involve both a direct effect and a gut microbiota-mediated pathway.

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Section: Mce Attenuated the Inammation In Rats With Colitiscontrasting

confidence: 43%

“…34 These ndings support the DSS-induced rat colitis model is suitable for studying human UC. The extract of Mori Cortex could alleviate the colitis symptoms.…”

mentioning

confidence: 61%

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Mori Cortex regulates P-glycoprotein in Caco-2 cells and colons from rats with experimental colitis via direct and gut microbiota-mediated mechanisms

et al. 2017

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“…CD is usually designated as a Th1 and Th17 condition with elevated production of IL-12, IL-23, IFN- γ , and IL-17, whereas UC is usually characterized as a Th2 and Th9 condition with increased production of IL-13, IL-5, and IL-9 [2]. The roles of cytokines in initiating, mediating, perpetuating, and controlling intestinal inflammation and tissue injury have been intensely studied because they are the key players in the pathogenesis of IBD and they may be the potential therapeutic targets [11, 13]. Antibodies against TNF, IL-12/IL-23p40, IFN- γ , IL-6R, IL-11, IL-13, IL-17A, integrin, and recombinant IL-10 and IFN- β have been tested or applied in clinics to treat IBD patients [11].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

Guan

Zhang

2017

Mediators of Inflammation

135

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Cytokines play an important role in the immunopathogenesis of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, where they drive and regulate multiple aspects of intestinal inflammation. The imbalance between proinflammatory and anti-inflammatory cytokines that occurs in IBD results in disease progression and tissue damage and limits the resolution of inflammation. Targeting cytokines have been novel strategies in the treatment of IBD. Recent studies show the beneficial effects of anticytokine treatments to IBD patients, and multiple novel cytokines are found to be involved in the pathogenesis of IBD. In this review, we will discuss the recent advances of novel biologics in clinics and clinical trials, and novel proinflammatory and anti-inflammatory cytokines found in IBD with focusing on IL-12 family and IL-1 family members as well as their relevance to the potential therapy of IBD.

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“…T cells are widely accepted to represent a central effector cell population not only driving and promoting but also containing tissue manifestation in IBD [6] . Given a number of controversial study results, the role of T cells within IBD pathogenesis is complex and overall remains only partly understood [6] . However, T cells are frequently detected within colitic tissue in IBD patients and were shown to mediate colitis in a number of pre-clinical murine colitis models.…”

Section: Introductionmentioning

confidence: 99%

Immunopathogenesis of IBD: Batf as a Key Driver of Disease Activity

Hildner

Punkenburg

Abendroth

2016

Dig Dis

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Background: Inflammatory bowel diseases (IBDs) represent a group of chronic immune-mediated disorders that are influenced by a genetic predisposition and additional environmental triggers. Genome-wide association studies strongly implicate that a number of immune system-related genetic variations are critically contributing to the initiation and promotion of intestinal inflammation. Especially the identification of the strong association of a series of single nucleotide polymorphisms including interleukin (IL)-23R, CCR6, signal transducer and activator of transcription 3 (Stat3) and Stat4 with IBD susceptibility point at a critical involvement of T cells and especially of IL-17a-producing Th17 cells in the immune pathogenesis of IBD. In line with this hypothesis, a series of preclinical studies have unequivocally established that T cells are key drivers of immune-mediated colitis. Interestingly, especially Th17 cells were identified to be highly prevalent in inflamed IBD tissues, a finding that seems to be functionally relevant as genetic inactivation studies in the mouse resulted in almost complete suppression of colitis development. Key Messages: While targeting Th17 cell differentiation regulating transcription factors, as retinoic acid-related orphan receptor gamma t (RORγt) is effective in preventing murine colitis, one concern of drugs targeting RORγt in a clinical setting represents the large body of murine data unambiguously demonstrating that additional pathways within and outside the immune system are equally RORγt-dependent increasing the risk of undesirable side effects. The AP1 transcription factor Batf (B cell-activating transcription factor) appears to exclusively regulate pathways within lymphocytes. Importantly, Batf represents a central regulator of Th17 cell development and is strongly upregulated within IBD-affected tissues. Employing 2 acute colitis models, we demonstrate in this study that Batf-expressing T cells are critical drivers of T cell-mediated colitis while in contrast to Stat3 loss of Batf does not affect intestinal epithelial cell homeostasis ex vivo. Conclusions: Targeting Batf in IBD emerges as an attractive therapeutic approach disabling colitogenic T cell activities while sparing off-target effects in the intestinal epithelial cell compartment.

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Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

Cited by 135 publications

References 171 publications

Mori Cortex regulates P-glycoprotein in Caco-2 cells and colons from rats with experimental colitis via direct and gut microbiota-mediated mechanisms

Mori Cortex regulates P-glycoprotein in Caco-2 cells and colons from rats with experimental colitis via direct and gut microbiota-mediated mechanisms

Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

Immunopathogenesis of IBD: Batf as a Key Driver of Disease Activity

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