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

Hyunkeun Song, Hyunjin Park, Jiyoung Kim, Gabin Park, Yeong Seok Kim, Sung Mok Kim, Daejin Kim, Su Kil Seo, Hyun Kyung Lee, Dae Ho Cho, Daeyoung Hur

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)187-193
Number of pages7
JournalImmunology Letters
Volume136
Issue number2
DOIs
Publication statusPublished - 2011 May 1
Externally publishedYes

Keywords

  • IDO
  • L-kynurenine
  • Natural killer cells
  • NKG2D
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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