TY - JOUR
T1 - Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma
AU - Higuchi, Hiroshi
AU - Yamakawa, Natsuko
AU - Imadome, Ken Ichi
AU - Yahata, Takashi
AU - Kotaki, Ryutaro
AU - Ogata, Jun
AU - Kakizaki, Masatoshi
AU - Fujita, Koji
AU - Lu, Jun
AU - Yokoyama, Kazuaki
AU - Okuyama, Kazuki
AU - Sato, Ai
AU - Takamatsu, Masako
AU - Kurosaki, Natsumi
AU - Alba, Syakira Mohamad
AU - Azhim, Azran
AU - Horie, Ryouichi
AU - Watanabe, Toshiki
AU - Kitamura, Toshio
AU - Ando, Kiyoshi
AU - Kashiwagi, Takao
AU - Matsui, Toshimitsu
AU - Okamoto, Akinao
AU - Handa, Hiroshi
AU - Kuroda, Masahiko
AU - Nakamura, Naoya
AU - Kotani, Ai
N1 - Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/6/7
Y1 - 2018/6/7
N2 - 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).
AB - 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).
UR - https://www.scopus.com/pages/publications/85048267475
UR - https://www.scopus.com/pages/publications/85048267475#tab=citedBy
U2 - 10.1182/blood-2017-07-794529
DO - 10.1182/blood-2017-07-794529
M3 - Article
C2 - 29685921
AN - SCOPUS:85048267475
SN - 0006-4971
VL - 131
SP - 2552
EP - 2567
JO - Blood
JF - Blood
IS - 23
ER -