Blocking the immunosuppressive axis with small interfering RNA targeting interleukin (IL)-10 receptor enhances dendritic cell-based vaccine potency

J. H. Kim, T. H. Kang, K. H. Noh, H. C. Bae, Y. H. Ahn, Y. H. Lee, Eun Young Choi, K. H. Chun, S. J. Lee, T. W. Kim

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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.

Original languageEnglish
Pages (from-to)180-189
Number of pages10
JournalClinical and Experimental Immunology
Volume165
Issue number2
DOIs
StatePublished - 1 Aug 2011

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Interleukin-10 Receptors
Vaccine Potency
Immunosuppressive Agents
Dendritic Cells
Small Interfering RNA
Interleukin-10
Interleukins
Papillomaviridae
Cytokines
Neoplasms
Cell Surface Receptors
Interleukin-12
Major Histocompatibility Complex

Keywords

  • Dendritic cell
  • IL-10 receptor
  • Immunosuppression
  • Immunotherapy
  • SiRNA

Cite this

Kim, J. H. ; Kang, T. H. ; Noh, K. H. ; Bae, H. C. ; Ahn, Y. H. ; Lee, Y. H. ; Choi, Eun Young ; Chun, K. H. ; Lee, S. J. ; Kim, T. W. / Blocking the immunosuppressive axis with small interfering RNA targeting interleukin (IL)-10 receptor enhances dendritic cell-based vaccine potency. In: Clinical and Experimental Immunology. 2011 ; Vol. 165, No. 2. pp. 180-189.
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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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Blocking the immunosuppressive axis with small interfering RNA targeting interleukin (IL)-10 receptor enhances dendritic cell-based vaccine potency. / Kim, J. H.; Kang, T. H.; Noh, K. H.; Bae, H. C.; Ahn, Y. H.; Lee, Y. H.; Choi, Eun Young; Chun, K. H.; Lee, S. J.; Kim, T. W.

In: Clinical and Experimental Immunology, Vol. 165, No. 2, 01.08.2011, p. 180-189.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Kim, J. H.

AU - Kang, T. H.

AU - Noh, K. H.

AU - Bae, H. C.

AU - Ahn, Y. H.

AU - Lee, Y. H.

AU - Choi, Eun Young

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AU - Lee, S. J.

AU - Kim, T. W.

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