miR-31 regulates interleukin 2 and kinase suppressor of ras 2 during T cell activation

Xue, Feng; Li, H; Zhang, Jia; Lu, Jianhua; Xia, Yuanqing; Xia, Qiang

doi:10.1038/gene.2012.58

Cited by 26 publications

(25 citation statements)

References 21 publications

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“…Consistent with our findings for mice, stimulation via the TCR induces miR-31 expression in human T cells 46 . Blocking miR-31 expression in human T cells might prove therapeutically useful for boosting immune responses during chronic viral infection.…”

Section: Discussionsupporting

confidence: 92%

“…Because CD8 + T cells progressively lose the ability to secrete the cytokines IL-2 and TNF and, finally, IFN-γ 40 during chronic viral infection, we assessed the functionality of antigen-specific CD8 + T cells in wild-type, Mir31 −/− and Mir31 fl/fl Cd4 Cre mice on day 28 or 30 after infection with LCMV clone 13. Splenocytes from infected mice were pulsed ex vivo with the peptides GP33 and GP276 (from LCMV glycoprotein) and NP396 (from LCMV nucleoprotein), followed by intracellular cytokine staining for IFN-γ, TNF and IL-2 in CD8 + T cells.…”

Section: Resultsmentioning

confidence: 99%

“…8b,d). It has been suggested that miR-31 promotes the secretion of IL-2 by T cells 40,41 . However, we did not observe differences in the secretion of IL-2 from wild-type, Mir31 −/− or Mir31 fl/fl Cd4 Cre CD8 + T cells in response to stimulation with LCMV peptide (data not shown), and stimulation with PMA plus ionomycin induced a similar frequency of IL-2 + CD4 + T cells and IL-2 + CD8 + T cells in all mouse strains (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

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The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection

et al. 2017

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During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease. This disease phenotype was explained by the presence of larger numbers of cytokine-secreting LCMV-specific CD8+ T cells in miR-31-deficent mice than in wild-type mice. Mechanistically, miR-31 increased the sensitivity of T cells to type I interferons, which interfered with effector T cell function and increased the expression of several proteins related to T cell dysfunction during chronic infection. These studies identify miR-31 as an important regulator of T cell exhaustion in chronic infection.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection

et al. 2017

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“…This repression is reversed upon T-cell activation that downregulates miR-181c expression [38]. By contrast, miR-31 was found to be upregulated upon TCR stimulation and to increase IL-2 production [39]. By directly targeting kinase suppressor of ras 2, a repressor of COT/TPI2 signaling, miR-31 was shown to enhance the activity of nuclear factor of activated T cells (NFAT), which in turn promotes IL-2 expression.…”

Section: Mirna Regulation Of Il-2mentioning

confidence: 99%

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 AS isoform (344 bp) may have a different biological half-life or transportability, leading to the decreased expression of TCRf mRNA and protein Tsuzaka et al, 2002). Since it has been reported that miRNA can repress the translational of multiple protein-coding mRNAs by sequence-specific binding to the 3¢UTR and may be associated with prognosis, it remains an open question whether miRNA has played a role in regulation mechanism (Gimenes-Teixeira et al, 2013;Xue et al, 2013). This finding indicates that the abnormal expression and dysfunction of the TCRf related to the 3¢UTR play a role in T-cell immune disorders.…”

Section: Introductionmentioning

confidence: 99%