Blocking the immunosuppressive axis with small interfering RNA targeting interleukin (IL)-10 receptor enhances dendritic cell-based vaccine potency
- Authors
- Kim, J. H.; Kang, T. H.; Noh, K. H.; Bae, H. C.; Ahn, Y-H.; Lee, Y-H.; Choi, E. Y.; Chun, K-H.; Lee, S-J.; Kim, T. W.
- Issue Date
- 8월-2011
- Publisher
- WILEY-BLACKWELL
- Keywords
- dendritic cell; IL-10 receptor; immunosuppression; immunotherapy; siRNA
- Citation
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY, v.165, no.2, pp.180 - 189
- Indexed
- SCIE
SCOPUS
- Journal Title
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY
- Volume
- 165
- Number
- 2
- Start Page
- 180
- End Page
- 189
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/111832
- DOI
- 10.1111/j.1365-2249.2011.04410.x
- ISSN
- 0009-9104
- Abstract
- Improving dendritic cell (DC) functions is highly promising for therapeutic intervention of diverse diseases, including cancer. Immunosuppressive cytokines such as interleukin (IL)-10 produced by DCs themselves (autocrine) and other regulatory immune cells (paracrine) down-regulate functional profiles of DCs through specific cell surface receptors such as IL-10R. Here, we tried to improve DC functions using small interfering RNA (siRNA) technology to block an IL-10R-mediated immunosuppressive axis. DCs modified with siRNA targeting against IL-10R or IL-10 (DC/siIL-10R or DC/siIL-10) led to up-regulation of major histocompatibility complex (MHC) class II, CD40 co-stimulatory molecule, and IL-12 proinflammatory cytokine after lipopolysacharide (LPS) stimulation compared to DC/siGFP. Notably, the LPS-induced functional profiles of DC/siIL-10R were strongly resistant to the addition of recombinant IL-10, which mimicked paracrine IL-10. In contrast, those of DC/siIL-10 were reversed by adding exogenous IL-10. Consistently, DC/siIL-10R generated more human papilloma virus (HPV) E7-specific CD8(+) T cells and stronger anti-tumour effects against E7-expressing TC-1 tumour cells in vaccinated mice than DC/siGFP, as well as DC/siIL-10. Taken together, these results provide the groundwork for future clinical translation of siRNA-mediated strategy targeting IL-10R to enhance DC-based vaccine potency.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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