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

Allergy, Asthma & Clinical Immunology

Yao Tang¹  Xiaolei Liu¹  Yuanyuan Guan¹  Lixin An¹  Yan Zhao¹  Yuemei Ma² 

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

[2]Department of Allergy, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

关键词: Asthma;    miRNA-221-5p;    RORγt;    SOCS1;    Th17/Treg;   

DOI  :  10.1186/s13223-021-00620-8

来源: Springer

【 摘 要 】

BackgroundThis 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.MethodsBALB/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.ResultsThe 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.ConclusionmiRNA-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.

【 授权许可】

CC BY