Dendritic Cells from Rheumatoid Arthritis Patient Peripheral Blood Induce Th17 Cell Differentiation via miR-363/Integrin α v/TGF-β Axis

Autor: Chengsong Cai, H. Xiang, Liquan Hong, Yuhua Liu, Ju-Zhen Yan, Lahong Zhang, X. Feng, F. Pan
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
T-Lymphocytes
Cellular differentiation
Gene Expression
Arthritis
T-Lymphocytes
Regulatory
Arthritis
Rheumatoid
0302 clinical medicine
Transforming Growth Factor beta
Cells
Cultured
medicine.diagnostic_test
biology
Reverse Transcriptase Polymerase Chain Reaction
Chemistry
Interleukin-17
Cell Differentiation
Forkhead Transcription Factors
hemic and immune systems
General Medicine
Middle Aged
030220 oncology & carcinogenesis
Female
Signal Transduction
Adult
Blotting
Western
Immunology
Integrin
CD11c
Enzyme-Linked Immunosorbent Assay
chemical and pharmacologic phenomena
Peripheral blood mononuclear cell
Flow cytometry
03 medical and health sciences
Immune system
medicine
Humans
ITGAV
Interleukin-6
Dendritic Cells
Integrin alphaV
medicine.disease
Coculture Techniques
CD11c Antigen
MicroRNAs
030104 developmental biology
Cancer research
biology.protein
Th17 Cells
Zdroj: Scandinavian Journal of Immunology. 85:441-449
ISSN: 0300-9475
DOI: 10.1111/sji.12550
Popis: Dendritic cells (DCs) are critical regulators of immune responses. This study was to observe the effect of DCs from peripheral blood on the differentiation of Th17 in patients with rheumatoid arthritis (RA). Peripheral blood samples were collected from 30 patients with RA and 20 healthy controls, respectively. Flow cytometry results showed that in contrast to Treg cells, the proportion of Th17 cells in T cells and the Th17/Treg ratio were both increased in patients with RA. The RT-PCR results showed that Foxp3、ROR γt and miR-363 expression in PBMC of patients with RA were reduced, but the ITGAV expression was increased, which was negatively related to miR-363 expression. IL-17, TGF-β and IL-6 levels detected by ELISA were increased in peripheral blood serum of patients with RA. Moreover, we noted that the CD11C+ αν+ /CD11C+ DCs ratio was obvious increased in patients with RA and has positive correlation to the Th17/Treg ratio. In cocultured system, Th17 cell differentiation was significantly inhibited in the presence of ITGF-β suggesting that Th17 cell differentiation was controlled by active TGF-β (aTGF-β). After DCs transfecting with miR-363 mimics and cocultured with T cells, Th17 cell number, IL-17 level and ROR-γt expression were significantly reduced in the presence of latent TGF-β (ITGF-β). In addition, the integrin αv protein expression was both reduced in the presence of aTGF-β or ITGF-β. These data demonstrated that DCs induced Th17 cell differentiation through miR-363/Integrin αv/TGF-β pathway in patients with RA.
Databáze: OpenAIRE
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