Details

Autor(en) / Beteiligte

• Higuchi, Hiroshi
• Yamakawa, Natsuko
• Imadome, Ken-Ichi
• Yahata, Takashi
• Kotaki, Ryutaro
• Ogata, Jun
• Kakizaki, Masatoshi
• Fujita, Koji
• Lu, Jun
• Yokoyama, Kazuaki
• Okuyama, Kazuki
• Sato, Ai
• Takamatsu, Masako
• Kurosaki, Natsumi
• Alba, Syakira Mohamad
• Azhim, Azran
• Horie, Ryouichi
• Watanabe, Toshiki
• Kitamura, Toshio
• Ando, Kiyoshi
• Kashiwagi, Takao
• Matsui, Toshimitsu
• Okamoto, Akinao
• Handa, Hiroshi
• Kuroda, Masahiko
• Nakamura, Naoya
• Kotani, Ai

Titel

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

Ist Teil von

• Blood, 2018-06, Vol.131 (23), p.2552-2567

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 EBV-encoded 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-α, 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 EBV+ B-cell lymphoma. •EBV-coding miRNAs are transferred from infected into noninfected cells by exosome to regulate the function for the tumorigenesis.•Production of EBV-coding miRNAs will be an excellent diagnostic marker to separate patients with EBV+ diffuse large B-cell lymphoma into 2 groups. [Display omitted]