Cutting Edge: A Variant of the <i>IL-23R</i> Gene Associated with Inflammatory Bowel Disease Induces Loss of MicroRNA Regulation and Enhanced Protein Production

Zwiers, Antonie; Kraal, Laurens; Kraan, Tineke C. T. M. van de Pouw; Würdinger, Thomas; Bouma, Gerd; Kraal, Georg

doi:10.4049/jimmunol.1101494

Cited by 101 publications

(56 citation statements)

References 25 publications

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“…This IL-22 secretion by ILCs is induced upon the production of IL-23 and IL-1b (34,35). Alternatively, a correlation between the susceptibility of inflammatory bowel disease and the IL-23R gene has been demonstrated, showing that a defect in IL-23 signaling can lead to intestinal inflammation (36,37). Alternatively, several inflammatory diseases, including inflammatory bowel disease, are shown to have higher levels of IL-22 in humans (22).…”

Section: Temporary Postnatal Inhibition Of Ra Signaling Affects Silt mentioning

confidence: 99%

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine

Goverse

Labão-Almeida²,

Ferreira³

et al. 2016

The Journal of Immunology

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Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR− and NCR+ ILC3 subsets in the small intestine of mice raised on a vitamin A–deficient diet. Additionally, the percentages of IL-22–producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR− ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A–deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid–related orphan receptor γt–Cre × RARα-DN mice had reduced numbers of NCR− and NCR+ ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid–related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines.

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Section: Temporary Postnatal Inhibition Of Ra Signaling Affects Silt mentioning

confidence: 99%

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine

Goverse

Labão-Almeida²,

Ferreira³

et al. 2016

The Journal of Immunology

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“…The rs10889677 variant in the 3'UTR region of IL-23R gene which led to a loss of binging capacity for let-7e and let-7f displayed increased expression of IL-23R [45] . It means this mutation sustained IL-23 signaling and contributed to chronicity of IBD.…”

Section: Mirnas Regulate Il-23/il-23r Pathwaymentioning

confidence: 99%

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review

Chen¹,

Ren²,

Shi³

2014

WJGP

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Inflammatory bowel disease (IBD) is believed to develop via a complex interaction between genetic, environmental factors and the mucosal immune system. Crohn's disease and ulcerative colitis are two major clinical forms of IBD. MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNA molecules, and evolutionary conserved in animals and plants. It controls protein production at the post-transcriptional level by targeting mRNAs for translational repression or degradation. MiRNAs are important in many biological processes, such as signal transduction, cellular proliferation, differentiation and apoptosis. Considerable attention has been paid on the key role of miRNAs in autoimmune and inflammatory disease, especially IBD. Recent studies have identified altered miRNA profiles in ulcerative colitis, Crohn's disease and inflammatory bowel diseaseassociated colorectal cancer. In addition, emerging data have implicated that special miRNAs which suppress functional targets play a critical role in regulating key pathogenic mechanism in IBD. MiRNAs were found involving in regulation of nuclear transcription factor kappa B pathway (e.g. , miR-146a, miR-146b, miR-122, miR-132, miR-126), intestinal epithelial barrier function (e.g. , miR-21, miR-150, miR-200b) and the autophagic activity (e.g. , miR-30c, miR-130a, miR-106b, miR-93, miR-196). This review aims at discussing recent advances in our understanding of miRNAs in IBD pathogenesis, their role as disease biomarkers, and perspective for future investigation and clinical application. Key words: Crohn's disease; Inflammatory bowel disease; MicroRNA; Treatment; Ulcerative colitis; Biomarker Core tip: MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules that post-transcriptionally regulate gene and protein expression. Recent studies have identified altered miRNA profiles in inflammatory bowel disease (IBD). Special miRNAs which suppress functional targets have been found to play a critical role in regulating key pathogenic mechanism in IBD. In this review, we discuss the possibility to use miRNAs as biomarkers and therapeutic target in IBD.Chen WX, Ren LH, Shi RH. Implication of miRNAs for inflammatory bowel disease treatment: Systematic review. World

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“…Recent studies have demonstrated miRNAs to be involved in inflammatory bowel disease (IBD) susceptibility, as polymorphisms in miRNA-binding sites affect the gene expression and thus seem to play a pivotal part in the pathogenesis of this chronic disorder [17,26] . Moreover, it has been found that miRNAs are differentially expressed in ulcerative colitis (UC) and Crohn's disease (CD) [27] , the two main forms of IBD.…”

Section: Introductionmentioning

confidence: 99%

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

Coskun¹

2013

WJG

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Author contributions: Coskun M and Bjerrum JT performed the experiments and data analysis, wrote the manuscript, and wrote the final revision of the article; Troelsen JT provided with analytical tools, intellectual input and advice; Olsen J provided with reagents and human tissue; Seidelin JB and Nielsen OH contributed to the conceptual design, drafting of the manuscript and revising it critically for important intellectual content; all authors approved the final submitted manuscript. Abstract AIM: To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflammatory bowel disease. METHODS:Colonic mucosal pinch biopsies from the descending part were obtained endoscopically from patients with active UC or CD, quiescent UC or CD, as well as healthy controls. Total RNA was isolated and miRNA expression assessed using the miRNA microarray Geniom Biochip miRNA Homo sapiens (Febit GmbH, Heidelberg, Germany). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIM-CA-P+12 software package (Umetrics, Umea, Sweden). The microarray data were subsequently validated by quantitative real-time polymerase chain reaction (qPCR) performed on colonic tissue samples from active UC patients (n = 20), patients with quiescent UC (n = 19), and healthy controls (n = 20). The qPCR results were analyzed with Mann-Whitney U test. In silico prediction analysis were performed to identify potential miRNA target genes and the predicted miRNA targets were then compared with all UC associated susceptibility genes reported in the literature. RESULTS:The colonic mucosal miRNA transcriptome differs significantly between UC and controls, UC and CD, as well as between UC patients with mucosal inflammation and those without. However, no clear differences in the transcriptome of patients with CD and controls were found. The miRNAs with the strongest differential power were identified (miR-20b, miR-99a, miR-203, miR-26b, and miR-98) and found to be upregulated more than a 10-fold in active UC as compared to quiescent UC, CD, and controls. Two miRNAs, miR-125b-1* and let-7e*, were up-regulated more than 5-fold in quiescent UC compared to active UC, CD, and controls. Four of the seven miRNAs (miR-20b, miR-98, miR-125b-1*, and let-7e*) were validated by qPCR and found to be specifically upregulated in patients with UC. Using in silico analysis we found several predicted pro-inflammatory target genes involved in various pathways, such as mitogen-activated protein kinase and cytokine signaling, which are both key signaling pathways in UC.

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Cutting Edge: A Variant of the IL-23R Gene Associated with Inflammatory Bowel Disease Induces Loss of MicroRNA Regulation and Enhanced Protein Production

Cited by 101 publications

References 25 publications

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

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Cutting Edge: A Variant of the IL-23R Gene Associated with Inflammatory Bowel Disease Induces Loss of MicroRNA Regulation and Enhanced Protein Production

Cited by 101 publications

References 25 publications

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

Contact Info

Product

Resources

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miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis