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MicroRNA-146a negatively regulates IL-33 in activated group 2 innate lymphoid cells by inhibiting IRAK1 and TRAF6

Genes & Immunity volume 21, pages 37–44 (2020)Cite this article

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Abstract

Type II innate lymphoid cells (ILC2) play a very important role in the pathogenesis of allergic asthma. This study aims to investigate whether miR-146a inhibition of asthma is related with interleukin (IL)-33 signaling path way in ILC2 and the underlying mechanisms. Asthma mice model was induced by ovalbumin. miRNA146a mimics was administrated to asthma mice or transfected to activated ILC2 purified from asthma mice lung. RT-PCR was used to detect miRNA146a level in lung tissue and ILC2. IL-5 and IL-13 levels in culture supernatant were detected by flow cytometry. Interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), signal transducer and activator of transcription 1 (STAT1) protein expression levels were detected by western blot. miR-146a directly inhibited ILC2 function and suppressed ILC2 proliferation both in vivo and in vitro. During stimulation of ILC2, miR-146a expression gradually increased with a decrease of cell proliferation. Modulation of ILC2 function by miR-146a may depend on IL-33/interleukin 1 receptor-like 1 (IL1RL1 or ST2) signaling through inhibiting IRAK1 and TRAF6.miR-146a can inhibit IRAK1 and TRAF6, downstream molecules of ST2 signal pathway, thereby negatively regulate IL-33/ST2-activated ILC2 to inhibit asthma. Targeting miR-146 maybe a novel strategy for the treatment of allergic asthma.

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Funding

The work was supported by Wuxi Science and Education Revitalization Project-Young Medical Talents (QNRC058).

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  1. These authors contributed equally: Beili Lyu, Zicheng Wei

Authors and Affiliations

  1. Department of Respiration, Affiliated Hospital of Jiangnan University, NO. 200 Huihe Road, 214000, Wuxi, Jiangsu, China

    Beili Lyu

  2. Department of Stomatology, Affiliated Hospital of Jiangnan University, NO. 200 Huihe Road, 214000, Wuxi, Jiangsu, China

    Zicheng Wei

  3. Department of Neurosurgery, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, No. 68 Zhongshan Road, Liangxi District, 214002, Wuxi, Jiangsu, China

    Lei Jiang

  4. Department of Respiratory Medicine, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, No.68 Zhongshan Road, Liangxi District, 214002, Wuxi, China

    Chenhui Ma & Shuguang Han

  5. Department of Rheumatology, Affiliated Hospital of Jiangnan University, NO. 200 Huihe Road, 214000, Wuxi, Jiangsu, China

    Guangxia Yang

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  1. Beili Lyu
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Correspondence to Shuguang Han.

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Lyu, B., Wei, Z., Jiang, L. et al. MicroRNA-146a negatively regulates IL-33 in activated group 2 innate lymphoid cells by inhibiting IRAK1 and TRAF6. Genes Immun 21, 37–44 (2020). https://doi.org/10.1038/s41435-019-0084-x

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