Knockout of microRNA-155 ameliorates the Th1/Th17 immune response and tissue injury in chronic rejection

Zhang, Anchen; Wang, Ke; Zhou, Cheng; Gan, Zheng; Ma, Dongxia; Sun, Yuan; Wu, Jie; Huang, Xintang; Ren, Lingyun; Deng, Peng; Wu, Chuangyan; Zhang, Yue; Ding, Xiangchao; Chen, Jiuling; Xia, Jiahong

doi:10.1016/j.healun.2016.04.018

Cited by 39 publications

(27 citation statements)

References 20 publications

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“…In contrast, Yan et al showed that miR-155 inhibition in experimental autoimmune myocarditis resulted in reducing the severity of disease and inhibiting the Th17 immune response [26]. Consistent with this finding, miR-155 −/mice with chronic and autoimmune inflammation presented with defective Th17 differentiation [27]. Therefore, we hypothesize that inhibition of dysregulated miRNAs might be a promising therapeutic strategy for Th17-induced allergic diseases.…”

Section: Discussionsupporting

confidence: 74%

Effect of Lactobacillus acidophilus KLDS 1.0738 on miRNA expression in in vitro and in vivo models of β-lactoglobulin allergy

Wang

et al. 2018

Bioscience, Biotechnology, and Biochemistry

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This study aims to investigate the correlation between the ability of L. acidophilus to modulate miRNA expression and prevent Th17-dominated β-lactoglobulin (β-Lg) allergy. In vitro immunomodulation was evaluated by measuring splenocyte proliferation, Th17-related immune response and miRNA expression in β-Lg-sensitized splenocytes cultured with live L. acidophilus. Next, the allergic mouse model was used to evaluate anti-allergy capability of lactobacilli. The β-Lg challenge led to induction of up-regulation of miR-146a, miR-155, miR-21 and miR-9 expression in both in vivo and in vitro, along with increased Th17-related cytokine levels and mRNA expression of RORγt and IL-17. However, treatment of live L. acidophilus significantly suppressed hypersensitivity responses and Th17 cell differentiation. Moreover, administration of live L. acidophilus reduced expression of four miRNAs, especially miR-146a and miR-155. In addition, the decreased expression of the miRNAs in the spleen of the L. acidophilus-treated group was closely associated with decrease of IL-17 and RORγt mRNA expression.

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Section: Discussionsupporting

confidence: 74%

Effect of Lactobacillus acidophilus KLDS 1.0738 on miRNA expression in in vitro and in vivo models of β-lactoglobulin allergy

Wang

et al. 2018

Bioscience, Biotechnology, and Biochemistry

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“…It is involved in immunosuppressive maintenance after transplantation and during tumor growth and pathogenic infection ( 11 , 14 , 15 ). In particular, miR155 has been found to be a prominent regulator of innate and adaptive immune responses ( 17 , 19 ) because it modulates DC maturation and function as well as allograft rejection after transplantation ( 18 , 20 , 54 , 55 ). In this study, we found that ectopic MALAT1 promoted DC-SIGN expression by functioning as an miR155 sponge in the cytoplasm, which is essential for the tolerogenic maintenance of DCs.…”

Section: Discussionmentioning

confidence: 99%

“…Most importantly, DC-SIGN actively contributes to the induction of allograft immune tolerance after transplantation ( 15 ). It has been reported that DC-SIGN is indirectly targeted by miR155, a prominent regulator of DC function and allograft immunity ( 16 – 20 ), via direct inhibition of PU.1 ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

The Long Noncoding RNA MALAT1 Induces Tolerogenic Dendritic Cells and Regulatory T Cells via miR155/Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Nonintegrin/IL10 Axis

Zhang

Yang

et al. 2018

Front. Immunol.

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By shaping T cell immunity, tolerogenic dendritic cells (tDCs) play critical roles in the induction of immune tolerance after transplantation. However, the role of long noncoding RNAs (lncRNAs) in the function and immune tolerance of dendritic cells (DCs) is largely unknown. Here, we found that the lncRNA MALAT1 is upregulated in the infiltrating cells of tolerized mice with cardiac allografts and activated DCs. Functionally, MALAT1 overexpression favored a switch in DCs toward a tolerant phenotype. Mechanistically, ectopic MALAT1 promoted dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) expression by functioning as an miR155 sponge, which is essential for the tolerogenic maintenance of DCs and the DC-SIGN-positive subset with more potent tolerogenic ability. The adoptive transfer of MALAT1-overexpressing DCs promoted cardiac allograft survival and protected from the development of experimental autoimmune myocarditis, accompanied with increasing antigen-specific regulatory T cells. Therefore, overexpressed MALAT1 induces tDCs and immune tolerance in heart transplantation and autoimmune disease by the miRNA-155/DC-SIGH/IL10 axis. This study highlights that the lncRNA MALAT1 is a novel tolerance regulator in immunity that has important implications in settings in which tDCs are preferred.

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“…Additionally, we speculate that this might prevent Th1 differentiation as the miR‐212~132 cluster has been shown to inhibit Stat4 , indirectly repressing Ifng . miR‐10b, miR‐210, miR‐155 and miR‐30a have been previously described to be involved in Th17 regulation and function, but are not significantly altered in our arrays.…”

Section: Discussionmentioning

confidence: 78%

microRNA cluster 106a~363 is involved in T helper 17 cell differentiation

Kästle

Bartel²,

Geillinger-Kästle³

et al. 2017

Immunology

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T-helper cell type 17 (Th17) mediated inflammation is associated with various diseases including autoimmune encephalitis, inflammatory bowel disease and lung diseases such as chronic obstructive pulmonary disease and asthma. Differentiation into distinct T helper subtypes needs to be tightly regulated to ensure an immunological balance. As microRNAs (miRNAs) are critical regulators of signalling pathways, we aimed to identify specific miRNAs implicated in controlling Th17 differentiation. We were able to create a regulatory network model of murine T helper cell differentiation by combining Affymetrix mRNA and miRNA arrays and in silico analysis. In this model, the miR-212~132 and miR-182~183 clusters were significantly up-regulated upon Th17 differentiation, whereas the entire miR-106~363 cluster was down-regulated and predicted to target well-known Th17 cell differentiation pathways. In vitro transfection of miR-18b, miR-106a and miR-363-3p into primary murine Cd4 lymphocytes decreased expression of retinoid-related orphan receptor c (Rorc), Rora, Il17a and Il17f, and abolished secretion of Th17-mediated interleukin-17a (Il17a). Moreover, we demonstrated target site-specific regulation of the Th17 transcription factors Rora and nuclear factor of activated T cells (Nfat) 5 by miR-18b, miR-106a and miR-363-3p through luciferase reporter assays. Here, we provide evidence that miRNAs are involved in controlling the differentiation and function of T helper cells, offering useful tools to study and modify Th17-mediated inflammation.

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Knockout of microRNA-155 ameliorates the Th1/Th17 immune response and tissue injury in chronic rejection

Cited by 39 publications

References 20 publications

Effect of Lactobacillus acidophilus KLDS 1.0738 on miRNA expression in in vitro and in vivo models of β-lactoglobulin allergy

Effect of Lactobacillus acidophilus KLDS 1.0738 on miRNA expression in in vitro and in vivo models of β-lactoglobulin allergy

The Long Noncoding RNA MALAT1 Induces Tolerogenic Dendritic Cells and Regulatory T Cells via miR155/Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Nonintegrin/IL10 Axis

microRNA cluster 106a~363 is involved in T helper 17 cell differentiation

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