title: IDO metabolite produced by EBV-transformed B cells inhibits surface expression of NKG2D in NK cells via the c-Jun N-terminal kinase (JNK) pathway.
abstract: Natural Killer cells are known to play a major role in the innate immune response against viral infections and tumor cells. Several viruses, such as CMV, EBV and HIV-1, have acquired strategies to escape elimination by NK cells. In this study, we observed that EBV infection increased expression of IDO on B cells. To evaluate the function of IDO associated with EBV infection, we investigated whether EBV-induced IDO could modulate expression of NK cell-activation receptor, NKG2D. When NK cells were co-incubated with EBV transformed B cells, surface expression of NKG2D was significantly reduced in NK cells. Incubation with L-kynurenine, an IDO metabolite, down-modulated NKG2D expression in NK cells in a dose- and time-dependent manner. Incubation with the JNK inhibitor SP600125 also inhibited NKG2D expression in NK cells. In addition, we observed that the effect of L-kynurenine was blocked by JNK agonist, anisomycin, suggesting the involvement of the JNK pathway in the signal transduction of L-kynurenine-reduced NKG2D expression. Furthermore, IL-18 significantly reduced L-kynurenine-induced down-regulation of NKG2D expression in NK cells. Taken together, these data indicate that down-regulation of NKG2D by EBV-induced IDO metabolite provides a potential mechanism by which EBV escapes NKG2D-mediated attack by immune cells.
authors.affiliation: Department of Anatomy, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Song
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Park
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Gabin
authors.initials: G
authors.lastname: Park
authors.forename: Yeong-Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Sung Mok
authors.initials: SM
authors.lastname: Kim
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.forename: Su Kil
authors.initials: SK
authors.lastname: Seo
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: DaeHo
authors.initials: D
authors.lastname: Cho
authors.forename: Daeyoung
authors.initials: D
authors.lastname: Hur
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D017077:Culture Media, Conditioned; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D055655:NK Cell Lectin-Like Receptor Subfamily K; D048031:JNK Mitogen-Activated Protein Kinases