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Circ_0067835 regulates allergic inflammatory response in type-2 innate lymphoid cells in allergic rhinitis (AR) via miR-155/GATA3

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Abstract

Allergic rhinitis (AR) is a familiar respiratory allergic inflammatory disease with higher incidence. The pathogenesis of AR is particularly complex. Therefore, a lot of work is acquired to excavate deep mechanisms, thereby providing effective strategies for AR diagnose and treatment. AR mice model was induced by recombinant murine IL-33 (0.05 µg/µl) on days 1, 3, and 5. The lentiviral vectors carrying si-circ_0067835, miR-155 mimic, si-NC or miR-NC were injected into AR mice. Thus, mice were divided into control, AR, AR + si-NC, AR + si-circ_0067835, AR + si-circ_0067835 + miR-NC, and AR + si-circ_0067835 + miR-155 mimic groups. qRT-PCR experiment was used to measure the expression of circ_0067835 and miR-155. Behavioral test result was quantified to assess AR mice model. Hematoxylin and eosin (HE) staining was performed to analyze histopathological changes. Helper T cell 2 (Th2) cytokines (IL-4, IL-5, IL-9 and IL-13) and percentage of type-2 innate lymphoid cells (ILC2s) in nasal mucosa tissues in AR mice model were evaluated needing western blot, ELISA, and flow cytometry. Besides, the targeting relationship between circ_0067835 and miR-155, or between miR-155 and GATA3, was investigated via luciferase report assay. Circ_0067835 expression levels were raised in the nasal mucosa tissues of AR mice. Inhibiting circ_0067835 could reduce Type2 cytokines and ILC2s levels in AR mice model. Furthermore, circ_0067835 targeted and positively regulated miR-155 expression, and GATA3 was a downstream target of miR-155 and adjusted by circ_0067835/miR-155 axis. In addition, silencing circ_0067835 inhibited cytokines and ILC2s levels by down-regulating miR-155. Circ_0067835 effectively inhibited AR response in ILC2s through participation of miR-155/GATA3 axis.

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Acknowledgements

This research was supported by National Natural Science Foundation of China (No.81760183), Jiangxi Provincial Natural Science Foundation (No. 20202ACBL206013), The Key Research and Development Program of Jiangxi Science and Technology Department (No. 20202BBGL73018) and the science and technology program of Jiangxi Provincial Education Department (GJJ200250).

Funding

This research was supported by National Natural Science Foundation of China (No.81760183), Jiangxi Provincial Natural Science Foundation (No. 20202ACBL206013), The Key Research and Development Program of Jiangxi Science and Technology Department (No. 20202BBGL73018) and the science and technology program of Jiangxi Provincial Education Department (GJJ200250).

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  1. Xunshuo Jiang and Taojian Huang are co-first authors.

Authors and Affiliations

  1. Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Nanchang, 330006, Jiangxi, China

    Xunshuo Jiang, Taojian Huang, Hongbing Liu, Xubo Chen, Hao Zhang, Ke Liu, Jianjian Deng & Chunping Yang

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Contributions

Guarantor of integrity of the entire study: CY. Study concepts: CY. Study design: definition of intellectual content: XJ. Literature research: JD. Clinical studies: HL. Experimental studies: TH. Data acquisition: KL. Data analysis: HZ. Statistical analysis: HZ. Manuscript preparation: XJ. Manuscript editing: XC. Manuscript review: CY.

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Correspondence to Chunping Yang.

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The animal usage protocols were approved in advance by the Animal Care and Use Committees of the Second Affiliated Hospital of Nanchang University.

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Jiang, X., Huang, T., Liu, H. et al. Circ_0067835 regulates allergic inflammatory response in type-2 innate lymphoid cells in allergic rhinitis (AR) via miR-155/GATA3. Human Cell 34, 1130–1141 (2021). https://doi.org/10.1007/s13577-021-00533-z

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