Genomic DNA Released by Dying Cells Induces the Maturation of APCs
Ken J. Ishii(Center for Biologics Evaluation and Research), Koichi Suzuki(National Institute of Diabetes and Digestive and Kidney Diseases), Cevayir Coban(Center for Biologics Evaluation and Research), Fumihiko Takeshita(Center for Biologics Evaluation and Research), Yasushi Itoh(National Institutes of Health), Hana Matoba(National Institute of Diabetes and Digestive and Kidney Diseases), Leonard D. Kohn(National Institute of Diabetes and Digestive and Kidney Diseases), Dennis M. Klinman(Center for Biologics Evaluation and Research)
Cited by 236Open Access
Abstract
Mature APCs play a key role in the induction of Ag-specific immunity. This work examines whether genomic DNA released by dying cells provides a stimulus for APC maturation. Double-stranded but not single-stranded genomic DNA triggered APC to up-regulate expression of MHC class I/II and various costimulatory molecules. Functionally, dsDNA enhanced APC function in vitro and improved primary cellular and humoral immune responses in vivo. These effects were dependent on the length and concentration of the dsDNA but were independent of nucleotide sequence. The maturation of APC induced by dsDNA may promote host survival by improving immune surveillance at sites of tissue injury/infection.
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