微小RNA-221-5p通过靶向细胞因子信号传导抑制因子1（SOCS1），经由维甲酸相关孤核受体γt/叉头框蛋白3（RORγt/Foxp3）抑制哮喘中的辅助性T细胞17/调节性T细胞（Th17/Treg）比例。

MiRNA-221-5p suppressed the Th17/Treg ratio in asthma via RORγt/Foxp3 by targeting SOCS1.

作者信息

Guan Yuanyuan, Ma Yuemei, Tang Yao, Liu Xiaolei, Zhao Yan, An Lixin

机构信息

Department of Allergy, First Affiliated Hospital of Harbin Medical University, 199 Dongdazhi Street, Nangang District, Harbin, 150001, Heilongjiang, China.

Department of Allergy, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Allergy Asthma Clin Immunol. 2021 Dec 4;17(1):123. doi: 10.1186/s13223-021-00620-8.

BACKGROUND

This study was designed to investigate the mechanism and effects of miRNA-221-5p on the T-helper 17 (Th17)/T-regulatory (Treg) ratio in asthma.

METHODS

BALB/c mice were intranasally challenged with 100 µg OVA on 14 and 21 day. Mice were rechallenged with 2.5% OVA-PBS on 22 and 28 day. Mice were sacrificed using on day 30 under 35 mg/kg pentobarbital sodium. PBMCs were induced vitro model of asthma using 500 ng of lipopolysaccharides (LPS) for 4 h.

RESULTS

The expression of miRNA-221-5p was reduced in in vivo model, compared sham group. The vitro model of asthma treated with miRNA-221-5p mimic resulted in the reduction of IL-6, IL-17, IL-21 and IL-22 levels, and induction of IL-10, IL-35 and TGF-β levels. In addition, down-regulation of miRNA-221-5p induced the protein expression of suppressor of cytokine signaling 1 (SOCS1) and receptor-related orphan receptor-gamma-t (RORγt) and suppressed that of FOXP3 in in vitro model of asthma. Over-expression of miRNA-221-5p induced the protein expression of FOXP3, and suppressed that of SOCS1 and RORγt in in vitro model of asthma. The inhibition of SOCS1 or RORγt attenuated the effects of anti-miRNA-221-5p on Th17/Treg ratio in asthma.

CONCLUSION

miRNA-221-5p may play critical roles in driving the differentiation of Th17/Treg ratio via RORγt/Foxp3 by Targeting SOCS1, reduced the function of Th17 cells by directly inhibiting RORγt/SOCS1 and promoted the function of Treg cells via Foxp3/ SOCS1 in asthma.

背景

本研究旨在探讨微小RNA-221-5p对哮喘中辅助性T细胞17（Th17）/调节性T细胞（Treg）比例的作用机制。

方法

在第14天和第21天，用100μg卵清蛋白（OVA）对BALB/c小鼠进行滴鼻激发。在第22天和第28天，用2.5%OVA-磷酸盐缓冲盐水（PBS）对小鼠进行再次激发。在第30天，使用35mg/kg戊巴比妥钠处死小鼠。使用500ng脂多糖（LPS）诱导外周血单个核细胞（PBMC）建立哮喘体外模型4小时。

结果

与假手术组相比，体内模型中微小RNA-221-5p的表达降低。用微小RNA-221-5p模拟物处理的哮喘体外模型导致白细胞介素-6（IL-6）、白细胞介素-17（IL-17）、白细胞介素-21和白细胞介素-22水平降低，并诱导白细胞介素-10、白细胞介素-35和转化生长因子-β（TGF-β）水平升高。此外，在哮喘体外模型中，微小RNA-221-5p的下调诱导细胞因子信号抑制因子1（SOCS1）和受体相关孤儿受体-γt（RORγt）的蛋白表达，并抑制叉头框蛋白P3（FOXP3）的蛋白表达。在哮喘体外模型中，微小RNA-221-5p的过表达诱导FOXP3的蛋白表达，并抑制SOCS1和RORγt的蛋白表达。抑制SOCS1或RORγt减弱了抗微小RNA-221-5p对哮喘中Th17/Treg比例的影响。