Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma

Higuchi, Hiroshi and Yamakawa, Natsuko and Imadome, Ken Ichi and Yahata, Takashi and Kotaki, Ryutaro and Ogata, Jun and Kakizaki, Masatoshi and Fujita, Koji and Lu, Jun and Yokoyama, Kazuaki and Okuyama, Kazuki and Sato, Ai and Takamatsu, Masako and Kurosaki, Natsumi and Mohamad Alba, Syakira and Azhim, Azran and Horie, Ryouichi and Watanabe, Toshiki and Kitamura, Toshio and Ando, Kiyoshi and Kashiwagi, Takao and Matsui, Toshimitsu and Okamoto, Akinao and Handa, Hiroshi and Kuroda, Masahiko and Nakamura, Naoya (2018) Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma. Blood, 131 (23). pp. 2552-2567. ISSN 0006-4971 E-ISSN 1528-0020

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Abstract

Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBVencoded RNA.We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-a, and arginase 1, suggesting the immune regulatory role of BART miRNAs.The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma.These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV1 B-cell lymphoma. (Blood. 2018;131(23):2552-2567).

Item Type:	Article (Journal)
Additional Information:	7380/65992
Uncontrolled Keywords:	Role of exosomes; Proinflammatory mediator; EBV-associated lymphoma
Subjects:	Q Science > Q Science (General) Q Science > QR Microbiology R Medicine > RC Internal medicine
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Allied Health Sciences
Depositing User:	Ir Dr Azran Azhim Noor Azmi
Date Deposited:	29 Aug 2018 17:00
Last Modified:	24 Jan 2019 15:47
URI:	http://irep.iium.edu.my/id/eprint/65992

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