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Functional characterization of a STAT3-dependent dendritic cell-derived CD14+ cell population arising upon IL-10-driven maturation.
- Source :
- OncoImmunology; Apr2013, Vol. 2 Issue 4, pe23837-1-e23837-14, 14p
- Publication Year :
- 2013
-
Abstract
- Interleukin (IL)-10 is a major cancer-related immunosuppressive factor, exhibiting a unique ability to hamper the maturation of dendritic cells (DCs). We have previously reported that IL-10 induces the conversion of activated, migratory CD1a<superscript>+</superscript> DCs found in the human skin to CD14<superscript>+</superscript>CD141<superscript>+</superscript> macrophage-like cells. Here, as a model of tumor-conditioned DC maturation, we functionally assessed CD14<superscript>-</superscript> and CD14<superscript>+</superscript> DCs that matured in vitro upon exposure to IL-10. IL-10-induced CD14<superscript>+</superscript> DCs were phenotypically characterized by a low maturation state as well as by high levels of BDCA3 and DC-SIGN, and as such they closely resembled CD14<superscript>+</superscript> cells infiltrating melanoma metastases. Compared with DC matured under standard conditions, CD14<superscript>+</superscript> DCs were found to express high levels of B7-H1 on the cell surface, to secrete low levels of IL- 12p70, to preferentially induce TH2 cells, to have a lower allogeneic TH cell and tumor antigen-specific CD8<superscript>+</superscript> T-cell priming capacity and to induce proliferative T-cell anergy. In contrast to their CD14<superscript>+</superscript> counterparts, CD14<superscript>-</superscript> monocyte-derived DCs retained allogeneic TH priming capacity but induced a functionally anergic state as they completely abolished the release of effector cytokines. Transcriptional and cytokine release profiling studies indicated a more profound angiogenic and pro-invasive signature of CD14<superscript>+</superscript> DCs as compared with DCs matured in standard conditions or CD14<superscript>-</superscript> DCs matured in the presence of IL-10. Importantly, signal transducer and activator of transcription 3 (STAT3) depletion by RNA interference prevented the development of the IL-10-associated CD14<superscript>+</superscript> phenotype, allowing for normal DC maturation and providing a potential means of therapeutic intervention. [ABSTRACT FROM AUTHOR]
- Subjects :
- INTERLEUKIN-10
CELL proliferation
DENDRITIC cells
MACROPHAGE activation
CYTOKINES
Subjects
Details
- Language :
- English
- ISSN :
- 21624011
- Volume :
- 2
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- 87520619
- Full Text :
- https://doi.org/10.4161/onci.23837