Toll-like receptor 9-independent suppression of skin inflammation by oligonucleotides

It has been well established that cytidine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) activate innate and adaptive immune responses in keratinocytes by stimulating Toll-like receptor 9 (TLR9)-dependent signaling pathways. However, as Dorn et al. report, keratinocytes possess another, yet uncharacterized, TLR9-independent mechanism for the recognition of ODNs. Surprisingly, the activation of the pathway leads to suppressed chemokine production in vitro and decreased skin inflammation in vivo.