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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >MicroRNA 15a/16‐1 suppresses aryl hydrocarbon receptor–dependent interleukin‐22 secretion in CD4 + + T cells and contributes to immune‐mediated organ injury
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MicroRNA 15a/16‐1 suppresses aryl hydrocarbon receptor–dependent interleukin‐22 secretion in CD4 + + T cells and contributes to immune‐mediated organ injury

机译：MicroRNA 15A / 16-1抑制CD4 + + T细胞中的芳基烃受体依赖性白细胞介素-22分泌物，并有助于免疫介导的器官损伤

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摘要

Interleukin‐22 (IL‐22), as a link between leukocytic and nonleukocytic cells, has gained increasing attention for its pronounced tissue‐protective properties. MicroRNAs, emerging as crucial immune modulators, have been reported to be involved in the production and action of various cytokines. However, the precise control of IL‐22 by microRNAs and its subsequent actions remained to be elucidated. In this study, we found a negative correlation between the expression of microRNA 15a/16‐1 (miR‐15a/16‐1) and IL‐22 in the model of concanavalin A–induced, immune‐mediated liver injury. Knockout of miR‐15a/16‐1 ameliorated liver injury in an IL‐22‐dependent manner. Further results revealed that cluster of differentiation 4–positive (CD4 + ) T cells were the major source of IL‐22 during liver injury and that the aryl hydrocarbon receptor was the direct target of miR‐15a/16‐1 in CD4 + T cells. In vivo and in vitro data showed that miR‐15a/16‐1 knockout CD4 + T cells produced more IL‐22, while overexpression of miR‐15a/16‐1 down‐regulated the IL‐22 production by inhibiting the aryl hydrocarbon receptor. Moreover, transfer of miR‐15a/16‐1 knockout CD4 + T cells promoted tissue repair compared to wild‐type CD4 + T cells by up‐regulating IL‐22. In addition, as a synergistic effect, IL‐22 could down‐regulate miR‐15a/16‐1 expression by activating phosphorylated signal transducer and activator of transcription 3‐c‐myc signaling, and the decrease of miR‐15a/16‐1 in damaged hepatocytes contributed to IL‐22‐mediated tissue repair by reducing cell apoptosis and promoting cell proliferation. As further proof, we demonstrated the role of miR‐15a/16‐1 in controlling IL‐22 production and IL‐22‐mediated reconstruction of the intestinal epithelial barrier in a dextran sodium sulfate–induced colitis model. Conclusion : Our results suggest that miR‐15a/16‐1 acts as a essential regulator of IL‐22 and that the miR‐15a/16‐1–aryl hydrocarbon receptor–IL‐22 regulatory axis plays a central role in tissue repair; modulation of miR‐15a/16‐1 might hold promise in developing new strategies to enhance IL‐22‐mediated tissue repair. (H epatology 2018;67:1027–1040)
机译：白细胞介素-22（IL-22）作为白细胞和非全核细胞之间的联系，对其明显的组织保护性能提高了越来越关注。据报道，MicroRNAS，作为至关重要的免疫调节剂，涉及各种细胞因子的生产和作用。然而，MicroRNA的IL-22的精确控制及其随后的作用仍有待阐明。在这项研究中，我们发现在康丹林A诱导的免疫介导的肝损伤模型中MicroRNA 15a / 16-1（miR-15a / 16-1）和IL-22的表达之间的负相关性。 MiR-15a / 16-1的敲除以IL-22依赖性方式改善肝损伤。进一步的结果表明，分化4-阳性（CD4 +）T细胞簇是肝损伤期间IL-22的主要来源，并且芳基烃受体是CD4 + T细胞中miR-15a / 16-1的直接靶标。体内和体外数据显示MiR-15A / 16-1敲除CD4 + T细胞产生更多IL-22，而通过抑制芳基烃受体，下调IL-15a / 16-1的过度抑制。 。此外，与Up-Catching IL-22相比，与野生型CD4 + T细胞相比，miR-15a / 16-1敲除CD4 + T细胞的转移。另外，作为协同效应，IL-22可以通过激活磷酸化信号传感器和转录3-C-MYC信号传导的活化剂来降低miR-15a / 16-1表达，以及M​​iR-15a / 16-1的减少在受损的肝细胞中，通过降低细胞凋亡和促进细胞增殖，导致IL-22介导的组织修复。作为进一步的证据，我们证明了miR-15a / 16-1在葡聚糖硫酸钠诱导的结肠炎模型中控制IL-22生产和IL-22介导的重建的IL-22生产和IL-22介导的重建。结论：我们的研究结果表明，miR-15a / 16-1作为IL-22的必需调节剂，MiR-15a / 16-1-芳基烃受体-i-22调节轴在组织修复中起着重要作用; MIR-15A / 16-1的调制可能在开发新的策略方面具有增强IL-22介导的组织修复的许可。 （H Popatology 2018; 67：1027-1040）

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  • 作者

    Lu Zhou; Liu Jiajing; Liu Xiaoming; Huang Enyu; Yang Jiao; Qian Jiawen; Zhang Dan; Liu Ronghua; Chu Yiwei;

  • 作者单位

    Department of Immunology School of Basic Medical Sciences and Institute of Biomedical;

    Department of Immunology School of Basic Medical Sciences and Institute of Biomedical;

    Department of Dermatology and Venereology Shenzhen HospitalPeking UniversityShenzhen China;

    Department of Immunology School of Basic Medical Sciences and Institute of Biomedical;

    Department of Immunology School of Basic Medical Sciences and Institute of Biomedical;

    Department of Immunology School of Basic Medical Sciences and Institute of Biomedical;

    Department of Immunology School of Basic Medical Sciences and Institute of Biomedical;

    Department of Immunology School of Basic Medical Sciences and Institute of Biomedical;

    Department of Immunology School of Basic Medical Sciences and Institute of Biomedical;

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  • 正文语种 eng
  • 中图分类 消化系及腹部疾病;
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