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

Cellular & Molecular Immunology volume 14, pages 276–284 (2017)Cite this article

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.

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Acknowledgements

We thank Ms. Nikki Phipps for support in preparing this article. We also thank Mr. Sandeep Dhaliwal in preparing the blood samples. Financial support provided by National Institutes of Health grant, DK39588 (M. Eric Gershwin).

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Author notes

  1. Takashi Tomiyama, Guo-Xiang Yang and Ming Zhao: Takashi Tomiyama, Guo-Xiang Yang, and Ming Zhao equally contributed to this work.

Authors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, 95616, CA, USA

    Takashi Tomiyama, Guo-Xiang Yang, Weici Zhang, Hajime Tanaka, Patrick SC Leung, Xiao-Song He & M Eric Gershwin

  2. Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka, 573-1191, Japan

    Takashi Tomiyama & Kazuichi Okazaki

  3. Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China

    Ming Zhao, Jing Wang & Qianjin Lu

  4. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan

    Hajime Tanaka

  5. Department of Microbiology, Monash University, Melbourne, Australia

    Ross L Coppel

  6. Division of Gastroenterology and Hepatology, University of California at Davis School of Medicine, Sacramento, 95817, CA, USA

    Christopher L Bowlus

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  1. Takashi Tomiyama
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Correspondence to Qianjin Lu or M Eric Gershwin.

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Tomiyama, T., Yang, GX., Zhao, M. et al. The modulation of co-stimulatory molecules by circulating exosomes in primary biliary cirrhosis. Cell Mol Immunol 14, 276–284 (2017). https://doi.org/10.1038/cmi.2015.86

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