Induction of regulatory dendritic cells by topical application of NF-kappaB decoy oligodeoxynucleotides.
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)-kappaB 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-kappaB decoy ODN modulate DC maturation with respect to their migration, phenotype, and cytokine profiles. Topical application of NF-kappaB 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-kappaB decoy ODN. During migration, NF-kappaB decoy-treated DC preferentially expressed inhibitory B7 molecules (i.e., B7-H1, B7-DC, and B7-H3) compared to OVA-sensitized DC without NF-kappaB decoy ODN, whereas co-stimulatory molecules (MHC class II, B7-1 and B7-2) were upregulated. Adoptive transfer of NF-kappaB 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.
Department of Geriatric and Environmental Dermatology, Nagoya City University, Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Iwao
I
Isomura
Yoichi
Y
Shintani
Yoko
Y
Yasuda
Kunio
K
Tsujimura
Akimichi
A
Morita
D019264:Adoptive Transfer; D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000628:therapy; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000235:genetics; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology*; D010047:Ovalbumin / Q000008:administration & dosage
D018122:B7-1 Antigen; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin