Induction of regulatory dendritic cells by topical application of NF-κB decoy oligodeoxynucleotides

Abstract

Dendritic cells (DC) have a key role in inducing an immune response, but DC in different maturation states are responsible for inducing tolerance. Topical application of nuclear factor (NF)-κB decoy oligodeoxynucleotides (ODN) induces antigen-specific peripheral tolerance in delayed-type hypersensitivity (DTH) to ovalbumin (OVA) by expanding CD4 +CD25 + regulatory T cells and by inhibiting DC migration. Herein we describe how topical NF-κB decoy ODN modulate DC maturation with respect to their migration, phenotype, and cytokine profiles. Topical application of NF-κB decoy ODN after OVA sensitization delayed the migration of Langerhans cells (LC) into draining lymph nodes, and morphologically mature LC remained in the peripheral tissue 2 days longer than in OVA-sensitized mice without application of NF-κB decoy ODN. During migration, NF-κB decoy-treated DC preferentially expressed inhibitory B7 molecules (i.e., B7-H1, B7-DC, and B7-H3) compared to OVA-sensitized DC without NF-κB decoy ODN, whereas co-stimulatory molecules (MHC class II, B7-1 and B7-2) were upregulated. Adoptive transfer of NF-κB decoy-treated DC inhibited DTH induction in prophylactic and therapeutic experiments. Inhibition of DTH by DC transfer was antigen-specific in vivo. This decoy ODN strategy might be useful for regulating immunity through DC.