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MiR-150-5p regulates the functions of type 2 innate lymphoid cells via the ICAM-1/p38 MAPK axis in allergic rhinitis

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Abstract

Type 2 innate lymphoid cells (ILC2s) exert an increasingly important influence on the pathological process of allergic rhinitis (AR), which is affected by microRNAs-mediated post-transcriptional regulation. This study aims to investigate the function of miR-150-5p in AR patients and the mouse model of AR. The mouse model of AR was established using the OVA challenge. The expressions of miR-150-5p, ICAM-1, p-p38 and p-GATA-3 were evaluated via RT-qPCR and western blot analysis. The level of ILC2s was examined with flow cytometry. Concentrations of OVA-specific IgE, IL-13 and IL-5 in serum were evaluated using ELISA. Histopathological examination was conducted through H&E staining. The interplay between ICAM-1 and miR-150-5p was determined through the DLR assay. The decreased miR-150-5p expression and increased ICAM-1, p-p38 and p-GATA-3 expressions and ILC2s levels were detected in AR patients and AR mice compared with controls. Treatment with miR-150-5p lentivirus alleviated AR symptoms (sneezing, rubbing, mucosa inflammation, serum type 2 cytokines and OVA-specific IgE) and lowered the ILC2s level in AR mice. MiR-150-5p was found to directly bind to 3′-UTR of ICAM-1 and downregulate ICAM-1 expression, thereby descending the level of p-p38, p-GATA-3 and suppressing ILC2s function to alleviate AR symptoms. Treatment with Lenti-ICAM-1 counteracted these protective effects of miR-150-5p. Upregulation of miR-150-5p repressed the ICAM-1/p38 axis which was vital to ILC2s development and function, thereby alleviating allergic symptoms of AR.

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Data availability

All datasets for the analysis in the present study are available upon reasonable request to the corresponding author.

Abbreviations

AR:

Allergic rhinitis

ICAM-1:

Intercellular cell adhesion molecule-1

LFA-1:

Leukocyte function-associated molecule

miRNAs:

MicroRNAs

NALT:

Nasal-associated lymphoid tissue

NC:

Negative control

OVA:

Ovalbumin

PBMCs:

Peripheral blood mononuclear cells

SPF:

Specific pathogen-free

Th2:

T-helper type 2

ILC2s:

Type 2 innate lymphoid cells

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Funding

This work was supported by the National Natural Science Foundation of China (Grant Number 8197150744).

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Authors and Affiliations

  1. Department of ENT, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No.42, Wenhua West Road, Lixia District, Jinan City, 250011, Shandong Province, China

    Lifeng Zhang, Wei Meng, Xiangjing Chen, Yunhong Ning, Meng Sun & Renzhong Wang

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  2. Wei Meng
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All authors gave final approval of the version to be published and agreed to be accountable for all aspects of this work.

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Correspondence to Renzhong Wang.

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The authors declared no commercial or financial conflict of interest.

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The study was approved by the Ethics Committee of The Affiliated Hospital of Shandong University of Traditional Chinese Medicine and obeyed the principles of the Declaration of Helsinki. The study protocol was approved by the Institutional Animal Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. The methodologies of this research were carried out following the National Institutes of Health guide for the care and use of laboratory animals.

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Zhang, L., Meng, W., Chen, X. et al. MiR-150-5p regulates the functions of type 2 innate lymphoid cells via the ICAM-1/p38 MAPK axis in allergic rhinitis. Mol Cell Biochem 477, 1009–1022 (2022). https://doi.org/10.1007/s11010-021-04346-4

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