MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis

Du, Changsheng; Liu, Chang; Kang, Jiuhong; Zhao, Guodong; Ye, Zhiqiang; Huang, Shichao; Li, Zhenxin; Wu, Zhi‐Ying; Pei, Gang

doi:10.1038/ni.1798

Cited by 722 publications

(590 citation statements)

References 41 publications

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“…As such, these miRNAs may be differentially expressed in other immunemediated diseases and have broader implications on CD4 T cell development and differentiation. It is well established that miRNAs play key roles in the development and function of Tregs (Gao et al, 2012;Josefowicz et al, 2012;Dooley et al, 2013), and differential expression of miRNAs have been found in patients with multiple sclerosis (Du et al, 2009;Keller et al, 2009;Otaegui et al, 2009;De Santis et al, 2010;Guerau-de-Arellano et al, 2011;Noorbakhsh et al, 2011;Jr OeF et al, 2012;Smith et al, 2012;Gandhi et al, 2013;Ridolfi et al, 2013;Søndergaard et al, 2013). To our knowledge none of the miRNAs identified in this study had been previously defined to play a role in Tregs.…”

Section: Discussionmentioning

confidence: 63%

“…While genetic studies have identified genes critical to the immune system as being potential risk factors (Baranzini et al, 2009b;De Jager et al, 2009;Beecham et al, 2013), many of the genetic contributors to this disease are unknown. An emerging area of interest in multiple sclerosis has been genetic regulation at the microRNA (miRNA) level (Du et al, 2009;Keller et al, 2009;Otaegui et al, 2009;De Santis et al, 2010;Guerau-de-Arellano et al, 2011;Noorbakhsh et al, 2011;Jr OeF et al, 2012;Smith et al, 2012;Gandhi et al, 2013;Ridolfi et al, 2013;Søndergaard et al, 2013). MiRNAs are small, non-coding RNA that regulate gene expression and, thus, modify cellular pathways and disease processes (Ambros, 2004;Bartel, 2004).…”

Section: Introductionmentioning

confidence: 99%

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MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis

Severin

Lee

Liu

et al. 2016

Brain

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis

Severin

Lee

Liu

et al. 2016

Brain

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“…Naive CD4ϩCD44Ϫ CD62Lϩ T cells were activated with anti-CD3 mAb (5 g/ml) and anti-CD28 mAb (2 g/ml) and were induced to differentiation according to the method described by Du et al, with slight modification (29). For Th1 cell differentiation, murine IL-12 (mIL-12; 10 ng/ml [Peprotech]) and anti-mIL-4 (10 g/ml; BD PharMingen) were added to the cultures; for Th2 cell differentiation, mIL-4 (40 ng/ml; eBioscience) and antimurine IFN␥ (anti-mIFN␥; 10 g/ml [eBioscience]) were added to the cultures; for inducible Treg cell differentiation, human transforming growth factor ␤1 (hTGF␤1; 10 ng/ml [Peprotech]) and mIL-2 (100 units/ml; BD PharMingen) plus anti-mIFN␥ (10 g/ml) were added to the cultures.…”

Section: Methodsmentioning

confidence: 99%

Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses

Hou¹,

He²,

Li³

et al. 2011

Arthritis & Rheumatism

111

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Objective. SM934, an artemisinin derivative, possesses potent antiproliferative and antiinflammatory properties. The aim of this study was to examine the effects and explore the mechanisms of SM934 to treat autoimmune disease in lupus-prone female MRL/lpr mice.Methods. In vitro, the effects of SM934 on the activation of polyclonal CD4؉ T cells and the differentiation of naive CD4؉ T cells were examined. In vivo, the preventative or therapeutic effects of SM934 in MRL/lpr mice were investigated. Ex vivo, the mechanisms of treatment were explored according to the immunologic correlates of disease.Results In female MRL/lpr mice, an autoimmune syndrome develops spontaneously that closely resembles human systemic lupus erythematosus (SLE) and is characterized by the production of various autoantibodies and the development of fatal glomerulonephritis (1,2).Disease begins as early as 8 weeks of age in these mice, with the presence of detectable serum autoantibodies. Pronounced lymphadenopathy is observed at 12 weeks of age, which is largely attributable to the accumulation of a population of B220ϩ and CD3ϩ cells that are mostly CD4Ϫ and CD8Ϫ (double-negative T cells). By 12-16 weeks of age, MRL/lpr mice begin to produce a variety of autoantibodies, including antidouble-stranded DNA (anti-dsDNA) antibodies. Multiple organs are affected, and a steady deterioration of renal function manifesting as severe proteinuria begins at approximately 16 weeks of age. From 16 weeks of age to 24 weeks of age, proliferative immune complex-

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“…Naïve CD4 1 T cells were isolated and then polarized to Th17 lineage in the presence of SAHA or DMSO as previously described. 32 Flow cytometry analysis of polarized T cells revealed that SAHA significantly suppressed the production of Th17 cells (Figure 3b), and western blot analysis indicated that SAHA reduced the expression of RORct and STAT3, and by which it promoted Foxp3 expression (Figure 3c). In line with these results, qPCR analysis further confirmed that SAHA downregulated the expression of IL-17A, IL-17F, STAT3 and RORct, but upregulated Foxp3 and CTLA-4 expressions (Figure 3d).…”

Section: Saha Prolongs the Survival Time Of Murine Cardiac Allograftsmentioning

confidence: 97%

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

et al. 2012

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Suberoylanilide hydroxamic acid (SAHA), as a histone deacetylase (HDAC) inhibitor (HDACi), was recently found to exhibit an immunosuppressive effect. However, whether SAHA can synergize with calcineurin inhibitors (CNIs) to inhibit allograft rejection and its underlying mechanism remain elusive. In this study, we demonstrated the synergistic effects of SAHA and non-therapeutic dose of tacrolimus (FK506) in prolonging the allograft survival in a murine cardiac transplant model. Concomitant intragraft examination revealed that allografts from SAHA-treated recipients showed significantly lower levels of IL-17 expression, and no discernable difference for IL-17 expressions was detected between SAHA-and SAHA/FK506-treated allograft as compared with allografts from FK506-treated animals. In contrast, administration of FK506 significantly suppressed interferon (IFN)-c but increased IL-10 expression as compared with that of SAHA-treated animals, and this effect was independent of SAHA. Interestingly, SAHA synergizes with FK506 to promote Foxp3 and CTLA4 expression. In vitro, SAHA reduced the proportion of Th17 cells in isolated CD4 1 T-cell population and decreased expressions of IL-17A, IL-17F, STAT3 and RORct in these cells. Moreover, SAHA enhances suppressive function of regulatory T (Treg) cells by upregulating the expression of CTLA-4 without affecting T effector cell proliferation, and increased the proportion of Treg by selectively promoting apoptosis of T effector cells. Therefore, SAHA, a HDACi, may be a promising immunosuppressive agent with potential benefit in conjunction with CNI drugs.

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MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis

Cited by 722 publications

References 41 publications

MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis

MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis

Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

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