The modulation of co-stimulatory molecules by circulating exosomes in primary biliary cirrhosis

• Published in: Cellular & molecular immunology Vol. 14; no. 3; pp. 276 - 284
• Main Authors: Tomiyama, Takashi, Yang, Guo-Xiang, Zhao, Ming, Zhang, Weici, Tanaka, Hajime, Wang, Jing, Leung, Patrick SC, Okazaki, Kazuichi, He, Xiao-Song, Lu, Qianjin, Coppel, Ross L, Bowlus, Christopher L, Gershwin, M Eric
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2017; Nature Publishing Group
• Subjects: Adult; Aged; Antibodies; Antigen-presenting cells; Antigen-Presenting Cells - metabolism; Antigens; Antigens, CD - metabolism; Autoimmune diseases; Autoimmunity; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; CD11c antigen; CD14 antigen; CD40 antigen; CD86 antigen; Cell activation; Chemokines; Cirrhosis; Cytokines; Cytokines - metabolism; Cytotoxicity; Dendritic cells; Epithelial cells; Exosomes; Exosomes - metabolism; Female; Gene Expression Profiling; Humans; Immunology; Inflammation Mediators - metabolism; Leukocytes, Mononuclear - metabolism; Liver cirrhosis; Liver Cirrhosis, Biliary - blood; Liver Cirrhosis, Biliary - genetics; Liver Cirrhosis, Biliary - metabolism; Liver diseases; Lymphocytes T; Male; Medical Microbiology; Microbiology; microRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Monocytes; Nanoparticles; Primary biliary cirrhosis; research-article; Vaccine; 共刺激分子; 原发性; 循环体; 肝硬化; 胆汁; 自身免疫性疾病; microRNA; autoimmunity; exosome; primary biliary cirrhosis
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2015.86

Exosomes are nanoparticles of endocytic origin, secreted by a myriad of cell populations that are attracting increased attention by virtue of their ability to modulate cell-to-cell communications. They are also attracting attention in a variety of immunological issues, including autoimmunity and, in particular, their ability to regulate cytokine and chemokine activation. Primary biliary cirrhosis （PBC） is considered a model autoimmune disease, which has a highly focused cytotoxic response against biliary epithelial cells. We have isolated exosomes from plasma from 29 patients with PBC and 30 healthy controls （HCs）, and studied the effect of these exosomes on co-stimulatory molecule expression and cytokine production in mononuclear cell populations using an ex vivo system. We also identified the microRNA （miRNA） populations in PBC compared to HC exosomes. We report herein that although exosomes do not change cytokine production, they do significantly alter co-stimulatory molecule expression on antigen-presenting populations. Further, we demonstrated that CD86 up-regulated expression on CD14＋ monocytes, whereas CD40 up-regulated on CD11c＋ dendritic cells by exosomes from patients with PBC. In addition, there were differences of miRNA expression of circulating exosomes in patients with PBC. These data have significant importance based on observations that co-stimulatory molecules play a differential role in the regulation of T-cell activation. Our observation indicated that aberrant exosomes from PBC selectively induce expression of co-stimulatory molecules in different subset of antigen-presenting cells. These alterations may involve in pathogenesis of autoimmune liver disease.