The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes

Stittrich, Anna-Barbara; Haftmann, Claudia; Sgouroudis, Evridiki; Kühl, Anja A.; Hegazy, Ahmed N.; Panse, Isabel; Riedel, René; Floßdorf, Michael; Dong, Jun; Fuhrmann, Franziska; Heinz, Gitta Anne; Fang, Zhuo; Li, Na; Bissels, Ute; Hatam, Farahnaz; Jahn, Angelina; Hammoud, Ben; Matz, Mareen; Schulze, Felix; Baumgrass, Ria; Bosio, Andreas; Mollenkopf, Hans-Joachim; Grün, Joachim R.; Thiel, Andreas; Chen, Wei; Höfer, Thomas; Loddenkemper, Christoph; Löhning, Max; Chang, Hyun‐Dong; Rajewsky, Nikolaus; Radbruch, Andreas; Mashreghi, Mir‐Farzin

doi:10.1038/ni.1945

Cited by 295 publications

(295 citation statements)

References 41 publications

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“…Although several miRNAs are reported to be regulated by Sirt1, such as miR-134 in the brain (34) and miR-138 in mammalian axon regeneration (35), the spectrum of Sirt1-regulated miRNAs in diabetic TG sensory neurons remains to be explored in detail. Previous studies proposed that miR-182 was implicated in multiple functional processes, such as oncogenesis and light/dark transition in the retina (36), T helper cell clonal expansion (37), and lipid homeostasis. miR-182 was recently reported to be tightly associated with metastasis of primary sarcomas (18) and ROS-induced premature senescence (38).…”

Section: Discussionmentioning

confidence: 99%

microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration

Wang

Zhao

et al. 2016

Diabetes

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Sensory neurons are particularly susceptible to neuronal damage in diabetes, and silent mating type information regulation 2 homolog 1 (Sirt1) has been recently identified as a key gene in neuroprotection and wound healing. We found that the expression of Sirt1 was downregulated in trigeminal sensory neurons of diabetic mice. A microRNA microarray analysis identified microRNA-182 (miR-182) as a Sirt1 downstream effector, and the expression level of miR-182 was increased by Sirt1 overexpression in trigeminal neurons; Sirt1 bound to the promoter of miR-182 and regulated its transcription. We also revealed that miR-182 enhanced neurite outgrowth in isolated trigeminal sensory neurons and overcame the detrimental effects of hyperglycemia by stimulating corneal nerve regeneration by decreasing the expression of one of its target genes, NOX4. Furthermore, the effects of miR-182 on corneal nerve regeneration are associated with a functional recovery of corneal sensation in hyperglycemic conditions. These data demonstrate that miR-182 is a key regulator in diabetic corneal nerve regeneration through targeting NOX4, suggesting that miR-182 might be a potential target for the treatment of diabetic sensory nerve regeneration and diabetic keratopathy.

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Section: Discussionmentioning

confidence: 99%

microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration

Wang

Zhao

et al. 2016

Diabetes

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“…Articles (14). Therefore, the downregulation of miR-182 might have special significance for LPS-induced immune response.…”

Section: Lps-induced Mirnas In Tlr Signalsmentioning

confidence: 99%

In vitro screening of LPS-induced miRNAs in leukocytes derived from cord blood and their possible roles in regulating TLR signals

2014

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“…In contrast to the T-cell receptor (TCR), whose impact on the expression of miRNAs has been investigated on a global miRNome-wide scale [19], a systematic analysis of how cytokines influence miRNA expression is still missing. Nonetheless, the available results emphasize a highly specific role for cytokines on modulating miRNA expression in T cells [20][21][22][23][24].TGF-β was shown to impact very specifically on the expression of several miRNAs and is a good example for the diverse action of a particular cytokine on miRNA expression in different T-cell subsets [21,22,25] (Fig. 1).…”

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confidence: 94%

Cross‐regulation between cytokine and microRNA pathways in T cells

et al. 2015

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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...

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The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes

Cited by 295 publications

References 41 publications

microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration

microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration

In vitro screening of LPS-induced miRNAs in leukocytes derived from cord blood and their possible roles in regulating TLR signals

Cross‐regulation between cytokine and microRNA pathways in T cells

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