miR‐155 deficiency protects mice from experimental colitis by reducing T helper type 1/type 17 responses

Singh, Udai P.; Murphy, Angela; Enos, Reilly T.; Shamran, Haidar A.; Singh, Narendra P.; Hong-quan, Guan; Hegde, Venkatesh L.; Fan, Daping; Price, Robert L.; Taub, Dennis D.; Mishra, Manoj K.; Nagarkatti, Mitzi

doi:10.1111/imm.12328

Cited by 110 publications

(97 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, human airway-infiltrating T cells from asthma patients have been shown to overexpress miR-19a, which promotes Th2 cytokine production, while conversely, its absence impairs Th2-cell responses [73]. Another example of an increase in the levels of a specific miRNA in association with inflammation is miR-155, which was found to be upregulated in inflammatory bowel disease (IBD), and miR-155 −/− mice displayed lower clinical scores and reduced systemic and mucosal Th1 and Th17 cytokines in an experimental colitis model [97]. miR-155 expression levels were also elevated in CD4 + T cells during EAE, and miR-155 −/− mice exhibited a delayed course of disease and reduced inflammation in the CNS when compared with WT controls [87,98].…”

Section: Inflammatory Pathology Associated With Dysregulated Mirna-cymentioning

confidence: 99%

Cross‐regulation between cytokine and microRNA pathways in T cells

et al. 2015

View full text Add to dashboard Cite

microRNA (miRNA) mediated regulation of protein expression has emerged as an important mechanism in T-cell physiology, from development and survival to activation, proliferation, and differentiation. One of the major classes of proteins involved in these processes are cytokines, which are both key input signals and major products of T-cell function. Here, we summarize the current data on the molecular cross-talk between cytokines and miRNAs: how cytokines regulate miRNA expression, and how specific miRNAs control cytokine production in T cells. We also describe the inflammatory consequences of deregulating the miRNA/cytokine axis in mice and humans. We believe this topical area will have key implications for immune modulation and treatment of autoimmune pathology. Keywords:Cytokines r Inflammation r miRNA r T cells microRNAs as regulators of protein expressionBiological processes require the integration of environmental stimuli at the level of gene expression. The robustness of genetic networks depends on the distinction between physiological responses (to particular cues) and biological "noise" (stochastic variations), which can be achieved, for example, by establishing feed-forward transcriptional loops. Over the past two decades, a new mechanism that interacts with transcriptional loops and sets additional thresholds, which enable cells to filter physiological signals from noise has emerged; this mechanism regulates gene expression at the posttranscriptional level and relies on microRNAs (miRNAs; reviewed in [1]). These are an abundant class of evolutionarily conserved small noncoding (untranslated) RNA species that control target mRNA stability, degradation, and translation, thus affecting the majority of mammalian genes [2].Correspondence: Dr. Anita Q. Gomes e-mail: anitagomes@medicina.ulisboa.ptIn the conventional miRNA biogenesis pathway, RNA polymerase II transcribed pri-miRNAs are processed by the nuclear RNase III enzyme Drosha (complexed with DGCR8) to generate 60-70 nt stem-loop intermediates, the pre-miRNAs, that are further processed into 19-24mers in the cytoplasm by another key RNase III, Dicer. Mature miRNAs are then incorporated into RNAinduced silencing complexes, whose core components are proteins of the Argonaute family (Ago1-4), which use the 5 end (nucleotides 2-8) "seed sequence" of the miRNA to recognize complementary mRNA transcripts (mostly in their 3 untranslated region) for deadenylation or inhibition of translation, ultimately resulting in mRNA decapping and decay (reviewed in [3,4]).Unique spatial and temporal expression patterns in distinct hematopoietic cell lineages are suggestive of multiple roles for miRNAs in hematopoiesis, self-tolerance, and in immune responses, which have been explored over the past decade (reviewed in [5,6]). Over a 100 different miRNAs have been shown to be expressed by cells of the immune system, where * These authors contributed equally to this work as first authors. * * These authors contributed equally to this work as last authors.C 2015 WILEY-VCH Ve...

show abstract

Section: Inflammatory Pathology Associated With Dysregulated Mirna-cymentioning

confidence: 99%

Cross‐regulation between cytokine and microRNA pathways in T cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…miR-155 has been found to promote the development of IBD. Its deficiency could abrogate intestinal inflammation in mice induced by dextran sodium sulfate (DSS) through decreasing the activation of Th1/Th17, CD11b + and CD11c + cells 18. Evidence has also indicated that miR-141 could alleviate experimental colitis by downregulating CXCL12β, which contributes to the leucocyte infiltration during inflammation 19.…”

Section: Introductionmentioning

confidence: 99%

miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD

Shi

et al. 2015

Gut

135

114

View full text Add to dashboard Cite

show abstract

“…Experimental colitis was induced using DSS as described previously (Singh et al, 2014; Singh et al, 2010). In brief, eight-week-old C57BL/6 naive group of mice received water alone, while mice in the colitic group received drinking water containing 3% DSS (MP Biomedical, LLC, Ohio) ad libitum for seven days.…”

Section: Methodsmentioning

confidence: 99%

Fatty acid amide hydrolase (FAAH) blockade ameliorates experimental colitis by altering microRNA expression and suppressing inflammation

Shamran

Singh

Zumbrun

et al. 2017

Brain, Behavior, and Immunity

Self Cite

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), which is thought to result from immune-mediated inflammatory disorders, leads to high morbidity and health care cost. Fatty acid amide hydrolase (FAAH) is an enzyme crucially involved in the modulation of intestinal physiology through anandamide (AEA) and other endocannabinoids. Here we examined the effects of an FAAH inhibitor (FAAH-II), on dextran sodium sulphate (DSS)-induced experimental colitis in mice. Treatments with FAAH-II improved overall clinical scores by reversing weight loss and colitis-associated pathogenesis. The frequencies of activated CD4+ T cells in spleens, mesenteric lymph nodes (MLNs), Peyer's patches (PPs), and colon lamina propiria (LP) were reduced by FAAH inhibition. Similarly, the frequencies of macrophages, neutrophils, natural killer (NK), and NKT cells in the PPs and LP of mice with colitis declined after FAAH blockade, as did concentrations of systemic and colon inflammatory cytokines. Microarray analysis showed that 26 miRNAs from MLNs and 217 from PPs had a 1.5-fold greater difference in expression after FAAH inhibition. Among them, 8 miRNAs were determined by reverse-transcription polymerase chain reaction (RT-PCR) analysis to have anti-inflammatory properties. Pathway analysis demonstrated that differentially regulated miRNAs target mRNA associated with inflammation. Thus, FAAH-II ameliorates experimental colitis by reducing not only the number of activated T cells but also the frequency of macrophages, neutrophils, and NK/NKT cell, as well as inflammatory miRNAs and cytokine at effector sites in the colon. These studies demonstrate for the first time that FAAH-II inhibitor may suppress colitis through regulation of pro-inflammatory miRNAs expression.

show abstract

miR‐155 deficiency protects mice from experimental colitis by reducing T helper type 1/type 17 responses

Cited by 110 publications

References 41 publications

Cross‐regulation between cytokine and microRNA pathways in T cells

Cross‐regulation between cytokine and microRNA pathways in T cells

miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD

Fatty acid amide hydrolase (FAAH) blockade ameliorates experimental colitis by altering microRNA expression and suppressing inflammation

Contact Info

Product

Resources

About