Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21

Autor: Xinyu Yang, Jianguang Wang, Huaijun Chen, Hao Zhong, Jiangang Zhang, Jinglan Ma, Yongsheng Li, Jianmin Wang, Tingting Zhang, Songfan Yan, Shengwei Jin, Qingqing Tian, Weiwei Sun
Rok vydání: 2018
Předmět:
0301 basic medicine
Adult
Male
Docosahexaenoic Acids
Immunology
Drug Evaluation
Preclinical
Arthritis
chemical and pharmacologic phenomena
Inflammation
T-Lymphocytes
Regulatory
General Biochemistry
Genetics and Molecular Biology
Arthritis
Rheumatoid
03 medical and health sciences
Young Adult
Immune system
Rheumatology
Downregulation and upregulation
RAR-related orphan receptor gamma
microRNA
medicine
Immunology and Allergy
Animals
Humans
Molecular Targeted Therapy
Cells
Cultured
Aged
Aged
80 and over
business.industry
FOXP3
hemic and immune systems
Cell Differentiation
Middle Aged
medicine.disease
Arthritis
Experimental
Up-Regulation
MicroRNAs
030104 developmental biology
Mice
Inbred DBA
Rheumatoid arthritis
Antirheumatic Agents
Case-Control Studies
Cytokines
Th17 Cells
medicine.symptom
Inflammation Mediators
business
Zdroj: Annals of the rheumatic diseases. 77(11)
ISSN: 1468-2060
Popis: ObjectiveTreg/Th17 imbalance plays an important role in rheumatoid arthritis (RA). Maresin 1 (MaR1) prompts inflammation resolution and regulates immune responses. We explored the effect of MaR1 on RA progression and investigated the correlation between MaR1 and Treg/Th17 balance.MethodsBoth patients with RA and healthy controls were recruited into the study. Collagen-induced arthritis (CIA) model was constructed to detect the clinical score, histopathological changes and Treg/Th17 ratio. Purified naive CD4+ T-cells were used to study the effect of MaR1 on its differentiation process and microRNA microarray studies were performed to investigate MaR1 downstream microRNAs in this process. MicroRNA transfection experiments were conducted by lentivirus to verify the mechanism of MaR1 on Treg/Th17 balance.ResultsCompared with controls, the MaR1 concentration was higher in the patients with inactive RA and lower in the patients with active RA. Expression of the Treg transcription factor FoxP3 was the highest in inactive RA and the lowest in active RA, while the Th17 transcription factor RORc showed a reverse trend. An inverse correlation was observed between the FoxP3/RORc ratio and Disease Activity Score 28. Intervention of MaR1 in the CIA model reduced joint inflammation and damage, and improved the imbalanced Treg/Th17 ratio. MaR1 increased Treg cells proportion while reduced Th17 cells proportion under specific differentiation conditions. Furthermore, miR-21 was verified as MaR1 downstream microRNA, which was upregulated by MaR1, modulating the Treg/Th17 balance and thus ameliorating the RA progression.ConclusionsMaR1 is a therapeutic target for RA, likely operating through effects on the imbalanced Treg/Th17 ratio found in the disease.
Databáze: OpenAIRE
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