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Updated: Jul 4, 2026

In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
Published on: January 22, 2020
Induction of regulatory dendritic cells by topical application of NF-kappaB decoy oligodeoxynucleotides
Iwao Isomura1, Yoichi Shintani, Yoko Yasuda
1Department of Geriatric and Environmental Dermatology, Nagoya City University, Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
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.
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.
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