title: The modulation of co-stimulatory molecules by circulating exosomes in primary biliary cirrhosis.
abstract: 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.Cellular & Molecular Immunology advance online publication, 21 September 2015; doi:10.1038/cmi.2015.86.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA.|Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka 573-1191, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tomiyama
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Guo-Xiang
authors.initials: GX
authors.lastname: Yang
authors.affiliation: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Weici
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA.|Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Patrick Sc
authors.initials: PS
authors.lastname: Leung
authors.affiliation: Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka 573-1191, Japan.
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: He
authors.affiliation: Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Microbiology, Monash University, Melbourne, Australia.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Coppel
authors.affiliation: Division of Gastroenterology and Hepatology, University of California at Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Bowlus
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA.
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D018836:Inflammation Mediators; D035683:MicroRNAs