MiR-381-3p Regulates the Antigen-Presenting Capability of Dendritic Cells and Represses Antituberculosis Cellular Immune Responses by Targeting CD1c

Wen, Qian; Zhou, Chaoying; Xiong, Wenjing; Su, Jing; He, Jiaxun; Zhang, Shimeng; Du, Xialin; Liu, Sudong; Wang, Jinli; Ma, Li

doi:10.4049/jimmunol.1500481

Cited by 20 publications

(15 citation statements)

References 33 publications

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“…Target genes of miR-381-3p are known to be involved in cellular processes and cellular macromolecule metabolism 23 . Notably, miR-381-3p mediates antigen-presenting ability in dendritic cells and anti-tuberculosis cellular immune responses by targeting CD1c 24 . In this study, we revealed that miR-381-3p directly targeted 3′ UTR of ETS2 and reduced the expression of ETS2.…”

Section: Discussionmentioning

confidence: 71%

RETRACTED: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome

Jiang

Zhu

et al. 2020

Molecular Therapy - Nucleic Acids

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Inflammatory mediators play a key role in the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, we aimed to explore the involvement of the Kcnq1 opposite strand/antisense transcript 1 (Kcnq1ot1)/miR-381-3p/E26 transformation-specific proto-oncogene 2 (ETS2) axis in inflammation of lipopolysaccharide (LPS)-induced ARDS. Microarray analysis revealed ETS2 as an upregulated gene in ARDS. Then, a LPS-induced ARDS mouse model was constructed, with a series of gain- or loss-of-function experiments conducted to evaluate the lung function and neutrophil extracellular trap (NET) formation in lung tissue and determine the neutrophil number, myeloperoxidase (MPO) activity, and inflammatory factor levels in bronchoalveolar lavage fluid (BALF). As the results revealed, downregulated expression of ETS2 resulted in improved lung function, decreased NETs, MPO activity, and levels of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), as well as increased IL-10 level. Then, the assays of dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and RNA pull-down were performed to validate that Kcnq1ot1 promoted ETS2 expression by competitively binding to miR-381-3p. Meanwhile, it was also found that Kcnq1ot1 silencing reversed the promotive effect of EST2 on ARDS. Our results provide evidence that Kcnq1ot1 silencing may reduce the inflammatory response in LPS-induced ARDS via inhibition of miR-381-30-dependent ETS2, thereby presenting new molecular understanding for the development of ARDS.

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Section: Discussionmentioning

confidence: 71%

RETRACTED: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome

Jiang

Zhu

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Previous studies have shown that miR-381-3p may be a target for the treatment of patients with TB or HIV-associated neurocognitive disorders 41 , 42 . To determine the clinical significance of miR-381-3p in patients with intestinal I/R injury, we measured the expression of miR-381-3p and associated proteins in ischemic intestinal tissues and normal tissues from clinical patients.…”

Section: Discussionmentioning

confidence: 99%

miR-381-3p knockdown improves intestinal epithelial proliferation and barrier function after intestinal ischemia/reperfusion injury by targeting nurr1

Liu

Yao

et al. 2018

Cell Death Dis

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Impairment in gut barrier function induced by intestinal ischemia/reperfusion (I/R) injury is associated with high morbidity and mortality. Intestinal barrier function requires the tight coordination of epithelial migration, proliferation and differentiation. We previously observed that nuclear receptor-related protein 1 (nurr1)-mediated proliferative pathway was impaired in intestinal I/R injury. Here, we aimed to assess the effect of nurr1 on intestinal barrier function and to evaluate microRNA (miRNA)-nurr1-mediated restoration of intestinal barrier function in intestinal I/R injury. We induced an in vivo intestinal I/R injury mouse model by clamping and then releasing the superior mesenteric artery. We also performed an in vitro study in which we exposed Caco-2 and IEC-6 cells to hypoxia/reoxygenation (H/R) conditions to stimulate intestinal I/R injury. Our results demonstrated that nurr1 regulated intestinal epithelial development and barrier function after intestinal I/R injury. miR-381-3p, which directly suppressed nurr1 translation, was identified by microarray and bioinformatics analysis. miR-381-3p inhibition enhanced intestinal epithelial proliferation and barrier function in vitro and in vivo and also attenuated remote organ injury and improved survival. Importantly, nurr1 played an indispensable role in the protective effect of miR-381-3p inhibition. Collectively, these findings show that miR-381-3p inhibition mitigates intestinal I/R injury by enhancing nurr1-mediated intestinal epithelial proliferation and barrier function. This discovery may lead to the development of therapeutic interventions for intestinal I/R injury.

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“…Interestingly, miR-301 was also up-regulated in T cells in the central nervous system of animals with experimental autoimmune encephalomyelitis ( Mycko et al, 2012 ), an animal model for the process of autoimmune demyelination occurring during multiple sclerosis, a disease with a possible association with HHV-6 infection ( Leibovitch and Jacobson, 2014 ). The up-regulated miR-101 and miR-381 are involved in the polarization and activation of the cells of the innate immune compartment, regulating the inflammatory response ( Zhu et al, 2010 ; Essandoh et al, 2016 ; Wen et al, 2016 ); the increased miR-548 may represent a mechanism facilitating viral pathogenesis as it negatively correlates with IFNγR1 levels ( Xing et al, 2014 ). miR-21 and miR-590, up-regulated by HHV-6A, are involved in differentiation and activation of T cells, particularly during autoimmunity ( Sousa et al, 2017 ), with miR-590 also down-regulating critical genes of signaling pathways similar in cancer and inflammation ( Sheikholeslami et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

HHV-6A/6B Infection of NK Cells Modulates the Expression of miRNAs and Transcription Factors Potentially Associated to Impaired NK Activity

et al. 2017

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Natural killer (NK) cells have a critical role in controlling virus infections, and viruses have evolved several mechanisms to escape NK cell functions. In particular, Human herpesvirus 6 (HHV-6) is associated with diseases characterized by immune dysregulation and has been reported to infect NK cells. We recently found that HHV-6 in vitro infection of human thyroid follicular epithelial cells and T-lymphocytes modulates several miRNAs associated with alterations in immune response. Since miRNAs are key regulators of many immune pathways, including NK cell functions, we aimed to study the impact of HHV-6A and -6B in vitro infection on the intracellular mediators correlated to NK cell function. To this purpose, a human NK cell line (NK-92) was infected in vitro with HHV-6A or 6B and analyzed for alterations in the expression of miRNAs and transcription factors. The results showed that both viruses establish lytic replication in NK-92 cells, as shown by the presence of viral DNA, expression of lytic transcripts and antigens, and by the induction of an evident cytopathic effect. Notably, both viruses, although with species-specific differences, induced significant modifications in miRNA expression of miRNAs known for their role in NK cell development, maturation and effector functions (miR-146, miR-155, miR-181, miR-223), and on at least 13 miRNAs with recognized role in inflammation and autoimmunity. Also the expression of transcription factors was significantly modified by HHV-6A/6B infection, with an early increase of ATF3, JUN and FOXA2 by both species, whereas HHV-6A specifically induced a 15-fold decrease of POU2AF1, and HHV-6B an increase of FOXO1 and a decrease of ESR1. Overall, our data show that HHV-6A and -6B infections have a remarkable effect on the expression of miRNAs and transcription factors, which might be important in the induction of NK cell function impairment, virus escape strategies and related pathologies.

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MiR-381-3p Regulates the Antigen-Presenting Capability of Dendritic Cells and Represses Antituberculosis Cellular Immune Responses by Targeting CD1c

Cited by 20 publications

References 33 publications

RETRACTED: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome

RETRACTED: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome

miR-381-3p knockdown improves intestinal epithelial proliferation and barrier function after intestinal ischemia/reperfusion injury by targeting nurr1

HHV-6A/6B Infection of NK Cells Modulates the Expression of miRNAs and Transcription Factors Potentially Associated to Impaired NK Activity

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