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The Journal of Immunology, 2003, 171: 2767.
Copyright © 2003 by The American Association of Immunologists

LETTERS TO THE EDITOR

Type I IFN Synthesis in Plasmacytoid Dendritic Cells

Sumiko Iho

Department of Immunology and Medical Zoology Fukui Medical University Fukui, Japan

Kerkmann et al. (1) recently reported two distinct pathways for IFN-{alpha} induction in human plasmacytoid dendritic cells (PDC), one dependent on and one independent of the IFNR-mediated feedback loop. However, the mechanisms by which the IFNR-mediated pathway is initiated were not mentioned. Concerning this matter, and because they did not make reference to our study (2), we provide here our results: Human PDC constitutively express IFN regulatory factor-7, and its enhancement and the nuclear-translocation by CpG DNA is preceded by p38 mitogen-activated protein kinase-dependent phosphorylation of STAT1. This pathway is triggered in a manner independent of autocrine response to IFN-{alpha}{beta}, thereby leading to the IFNR-mediated response to produce a vast amount of IFN-{alpha}. The sequence of the active motif we used is GACGATCGTC, which also exists in CpG-A (ODN 2216) that Kerkmann et al. used. This motif was originally reported by Kuramoto et al. (3) in mice, as possessing a potent immunostimulatory activity especially when flanked by poly (G) sequence; and has now been revealed to have outstanding activity in humans, as well. The ability of this sequence to directly activate the IFNR-independent pathway would help in elucidating the mechanisms of IFN-{alpha} production in PDC and designing the CpG DNA as a therapeutic drug.

References

  1. Kerkmann, M., S. Rothenfusser, V. Hornung, A. Towarowski, M. Wagner, A. Sarris, T. Giese, S. Endres, G. Hartmann. 2003. Activation with CpG-A and CpG-B oligonucleotides reveals two distinct regulatory pathways of type I IFN synthesis in human PDC. J. Immunol. 170:4465.[Abstract/Free Full Text]
  2. Takauji, R., S. Iho, H. Takatsuka, S. Yamamoto, T. Takahashi, H. Kitagawa, H. Iwasaki, R. Iida, T. Yokochi, T. Matsuki. 2002. CpG-DNA-induced IFN-{alpha} production involves p38 MAPK-dependent STAT1 phosphorylation in human plasmacytoid dendritic precursors. J. Leukocyte Biol. 72:1011.[Abstract/Free Full Text]
  3. Kuramoto, E., O. Yano, Y. Kimura, M. Baba, T. Makino, S. Yamamoto, T. Yamamoto, T. Kataoka, T. Tokunaga. 1992. Oligonucleotide sequences required for natural killer cell activation. Jpn. J. Cancer Res. 83:1128.[Medline]




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