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Cited by 340

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The Roles of Toll-Like Receptor 9, MyD88, and DNA-Dependent Protein Kinase Catalytic Subunit in the Effects of Two Distinct CpG DNAs on Dendritic Cell Subsets

Hemmi, Hiroaki, Kaisho, Tsuneyasu, Takeda, Kiyoshi, Akira, Shizuo·2003·The Journal of Immunology

Abstract

Oligodeoxynucleotides containing unmethylated CpG motifs (CpG DNAs) can function as powerful immune adjuvants by activating APC. Compared with conventional phosphorothioate-backbone CpG DNAs, another type of CpG DNAs, called an A or D type (A/D-type), possesses higher ability to induce IFN-α production. Conventional CpG DNAs can exert their activity through Toll-like receptor 9 (TLR9) signaling, which depends on a cytoplasmic adapter, MyD88. However, it remains unknown how A/D-type CpG DNAs exhibit their immunostimulatory function. In this study we have investigated murine dendritic cell (DC) responses to these two distinct CpG DNAs. Not only splenic, but also in vitro bone marrow-derived, DCs could produce larger amounts of IFN-α in response to A/D-type CpG DNAs compared with conventional CpG DNAs. This IFN-α production was mainly due to the B220+ DC subset. On the other hand, the B220− DC subset responded similarly to both CpG DNAs in terms of costimulatory molecule up-regulation and IL-12 induction. IFN-α, but not IL-12, induction was dependent on type I IFN. However, all activities of both CpG DNAs were abolished in TLR9- and MyD88-, but were retained in DNA-PKcs-deficient DCs. This study demonstrates that the TLR9-MyD88 signaling pathway is essential for all DC responses to both types of CpG DNAs.

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Metadata

Authors
Hemmi, H., Kaisho, T., Takeda, K., & Akira, S.
Venue
The Journal of Immunology
Published
2003-03
Volume
170
Issue
6
Pages
3059-3064
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1710348905
Cited by
340
References
36
FWCI
12.79
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: The Roles of Toll-Like Receptor 9, MyD88, and DNA-Dependent Protein Kinase Catalytic Subunit in the Effects of Two Distinct CpG DNAs on Dendritic Cell Subsets. https://app.cochat.ai/papers/10.4049/jimmunol.170.6.3059
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Hemmi, H., Kaisho, T., Takeda, K., & Akira, S. (2003). The Roles of Toll-Like Receptor 9, MyD88, and DNA-Dependent Protein Kinase Catalytic Subunit in the Effects of Two Distinct CpG DNAs on Dendritic Cell Subsets. The Journal of Immunology. https://doi.org/10.4049/jimmunol.170.6.3059

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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