title: Blocking the immunosuppressive axis with small interfering RNA targeting interleukin (IL)-10 receptor enhances dendritic cell-based vaccine potency.
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.
authors: Division of Infection and Immunology, Graduate School of Medicine, Korea University, Seoul, Korea.
authors: J H
authors: JH
authors: Kim
authors: T H
authors: TH
authors: Kang
authors: K H
authors: KH
authors: Noh
authors: H C
authors: HC
authors: Bae
authors: Y-H
authors: YH
authors: Ahn
authors: Y-H
authors: YH
authors: Lee
authors: E Y
authors: EY
authors: Choi
authors: K-H
authors: KH
authors: Chun
authors: S-J
authors: SJ
authors: Lee
authors: T W
authors: TW
authors: Kim
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