MicroRNA as Regulator of the Th17 Inflammation in Behcet's disease

BACKGROUND: MicroRNAs (miRNAs) play a critical role in the regulation of host genomic expression; they are also involved in regulation of the immune response by control of target genes. Recent studies of miRNAs have revealed that aberrant expression and/or function of miRNAs in chronic inflammatory and autoimmune diseases. To date, microRNA-155 (miR-155) is one of the most highly implicated miRNAs in autoimmunity. Behcet’s disease (BD) is a chronic inflammatory disease with autoimmune nature, characterized by oral and genital ulcers and ocular inflammation. Although the pathogenesis of BD is largely unknown, it has been reported recently that autoimmune and autoinflammation are complicatedly involved. PURPOSE: The aim of this study was to investigate the contribution of miR-155 and its potential target in the pathogenesis of Behçet’s disease (BD). METHODS: The study population consisted of 46 patients with active and inactive BD, 18 patients with recurrent aphthous ulcer (RAU) as disease control and 19 healthy controls (HC). To verify Th17 inflammation in BD patients, IL-17 expression was measured using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and real-time polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMCs) with or without Th17 differentiation condition. The expression of miR-155 was also investigated using real-time PCR in PBMCs and isolated CD4+ T cells. Luciferase reporter assay and western blotting were carried out to determine whether Ets-1 is a target of miR-155. Subsequently, Ets-1 expression was quantified using real-time PCR in patients and controls. Western blotting was also performed to investigate the relationship between Ets-1 and IL-17 in patients with active BD and healthy controls. The effect of miR-155 on Th17 polarization was determined by flow cytometry and ELISA by using cells transfected with a miR-155 mimic or inhibitor RESULTS: The expression of miR-155 and IL-17 was significantly increased in CD4+ T cells of patients with active BD. A luciferase reporter assay revealed that Ets-1 was a target gene of miR-155, which was confirmed by western blotting. Furthermore, the expression of Ets-1 was inversely correlated with IL-17 in patients with active BD. More importantly, repression of miR-155 in CD4+ T cells increased Ets-1 expression and reduced the number of IL-17-expressing T cells and IL-17 production. CONCLUSION: This study revealed that miR-155 regulates the Th17 immune response by targeting Ets-1. Suppression of miR-155 reduced pathogenic IL-17-expressing T cells and may be a potential therapeutic strategy in BD.

Author dc:creator

• 나, 소영

Contributors dc:contributor

• 이, 은소
• 대학원 의학과
• 108154

• Behçet’s disease
• Th17 cells
• microRNA-155
• Ets-1
• 베체트병
• Th17 세포
• 마이크로 RNA-155

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000015038
000000015038

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/8661