Circulating Exosomal miR-17 Inhibits the Induction of Regulatory T Cells via Suppressing TGFBR II Expression in Rheumatoid Arthritis

• Published in: Cellular physiology and biochemistry Vol. 50; no. 5; pp. 1754 - 1763
• Main Authors: Wang, Liping, Wang, Chunyan, Jia, Xuqiang, Yu, Jing
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.11.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: 3' Untranslated Regions; Adult; Aged; Antagomirs - metabolism; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - pathology; Cancer; Case-Control Studies; Cell Differentiation; DNA methylation; Exosome; Exosomes - metabolism; Female; Flow cytometry; Gene expression; Homeostasis; Humans; Lymphocytes; Male; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - blood; MicroRNAs - metabolism; Middle Aged; miR-17; Original Paper; Pathogenesis; Polyethylene glycol; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta - antagonists & inhibitors; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Rheumatoid arthritis; RNA Interference; RNA, Small Interfering - metabolism; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tetraspanin 29 - metabolism; TGFBR II; Treg cells; United Kingdom > UK; China; miR-17; Treg cells; Exosome; TGFBR II; Rheumatoid arthritis
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000494793

Background/Aims: A reduced prevalence of circulating regulatory T cells (Tregs)is a hallmark of inflammatory rheumatoid arthritis (RA). However, the underlying mechanisms of alterations of Tregs are unclear. Methods: The ratio of Tregs in peripheral blood of healthy controls (HCs) and patients with RA was determined by flow cytometry. MicroRNA (miRNA) expression profiles in exosomes derived from RA patients (RA-exosomes) and in those from HCs (HC-exosomes) were detected by microarray analysis, and miR-17 was measured by quantitative real-time PCR. Transforming growth factor beta receptor II (TGFBR II) expressed by T cells was measured by flow cytometry. The interaction between miR-17 and TGFBR II was evaluated by dual-luciferase reporter assay. Results: We found that RA-exosomes can selectively affect Treg differentiation in vitro. Several miRNAs are more abundant in the RA-exosomes than in HC-exosomes. Among those upregulated in patients with RA, miR-17 can suppress Treg induction by inhibiting the expression of TGFBR II. Conclusion: Our findings imply that altered miRNA expression in RA-exosomes may contribute to the pathogenesis of RA by disrupting the homeostasis of Tregs.