Kerkmann et al. (1) recently reported two distinct pathways for IFN-α 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-αβ, thereby leading to the IFNR-mediated response to produce a vast amount of IFN-α. 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-α production in PDC and designing the CpG DNA as a therapeutic drug.
- Copyright © 2003 by The American Association of Immunologists
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