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10.1371/journal.pone.0200546

http://scihub22266oqcxt.onion/10.1371/journal.pone.0200546
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suck abstract from ncbi


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pmid29995930
      PLoS+One 2018 ; 13 (7 ): e0200546
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  • Epstein-Barr virus DNA modulates regulatory T-cell programming in addition to enhancing interleukin-17A production via Toll-like receptor 9 #MMPMID29995930
  • Salloum N ; Hussein HM ; Jammaz R ; Jiche S ; Uthman IW ; Abdelnoor AM ; Rahal EA
  • PLoS One 2018[]; 13 (7 ): e0200546 PMID29995930 show ga
  • Infection with the Epstein-Barr virus (EBV) has been associated with several autoimmune diseases including rheumatoid arthritis (RA). We have previously reported that DNA from this virus enhances production of the pro-autoimmune interleukin 17A (IL-17A) in mice. In this study we assessed the effect of EBV DNA on regulatory T cell programming and examined whether it mediated its effects via Toll-like receptor 9 (TLR9) in mice; moreover, we evaluated whether EBV DNA in humans had similar effects to those seen in mice. For this purpose, we assessed the linearity of the correlation between EBV DNA and IL-17A levels in RA subjects and matched controls. A modulatory effect for the viral DNA was observed for regulatory T cell markers with an inhibitory effect observed for CTLA4 expression in the EBV DNA-treated mice. To examine whether TLR9 mediated the detection of EBV DNA and enhancement of IL-17A production, mouse peripheral blood mononuclear cells were treated with the DNA in the presence or absence of the TLR9 inhibitor ODN 2088. Subsequently, IL-17A production from these cells was assessed. Treatment with the TLR9 inhibitor resulted in a significant decrease in IL-17A production indicating that TLR9 is involved in this pathway. In human subjects, examining the linearity of the correlation between EBV DNA and IL-17A levels in RA subjects showed a propensity for linearity that was not observed in controls. Our data thus indicates that EBV DNA itself acts as a modulator of the Th17 compartment as well as that of regulatory T cell mechanisms. The involvement of TLR9 in the EBV DNA-triggered induction of IL-17A suggests therapeutic targeting of this endosomal receptor in EBV positive subjects with an autoimmune flare-up or possibly for prophylactic purposes.
  • |Animals [MESH]
  • |DNA, Viral/*immunology [MESH]
  • |Female [MESH]
  • |Herpesvirus 4, Human/*immunology [MESH]
  • |Interleukin-17/*immunology [MESH]
  • |Mice [MESH]
  • |Mice, Inbred BALB C [MESH]
  • |T-Lymphocytes, Regulatory/*immunology/pathology [MESH]


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