Cargando…
Functional characterization of a STAT3-dependent dendritic cell-derived CD14(+) cell population arising upon IL-10-driven maturation
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(+) DCs found in the human skin to CD14(+)CD141(+) macropha...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Landes Bioscience
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654600/ https://www.ncbi.nlm.nih.gov/pubmed/23734330 http://dx.doi.org/10.4161/onci.23837 |
_version_ | 1782269593939607552 |
---|---|
author | Lindenberg, Jelle J. van de Ven, Rieneke Lougheed, Sinéad M. Zomer, Anoek Santegoets, Saskia J.A.M. Griffioen, Arjan W. Hooijberg, Erik van den Eertwegh, Alfons J.M. Thijssen, Victor L. Scheper, Rik J. Oosterhoff, Dinja de Gruijl, Tanja D. |
author_facet | Lindenberg, Jelle J. van de Ven, Rieneke Lougheed, Sinéad M. Zomer, Anoek Santegoets, Saskia J.A.M. Griffioen, Arjan W. Hooijberg, Erik van den Eertwegh, Alfons J.M. Thijssen, Victor L. Scheper, Rik J. Oosterhoff, Dinja de Gruijl, Tanja D. |
author_sort | Lindenberg, Jelle J. |
collection | PubMed |
description | 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(+) DCs found in the human skin to CD14(+)CD141(+) macrophage-like cells. Here, as a model of tumor-conditioned DC maturation, we functionally assessed CD14(-) and CD14(+) DCs that matured in vitro upon exposure to IL-10. IL-10-induced CD14(+) 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(+) cells infiltrating melanoma metastases. Compared with DC matured under standard conditions, CD14(+) 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(+) T-cell priming capacity and to induce proliferative T-cell anergy. In contrast to their CD14(+) counterparts, CD14(-) 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(+) DCs as compared with DCs matured in standard conditions or CD14(−) 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(+) phenotype, allowing for normal DC maturation and providing a potential means of therapeutic intervention. |
format | Online Article Text |
id | pubmed-3654600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Landes Bioscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-36546002013-06-03 Functional characterization of a STAT3-dependent dendritic cell-derived CD14(+) cell population arising upon IL-10-driven maturation Lindenberg, Jelle J. van de Ven, Rieneke Lougheed, Sinéad M. Zomer, Anoek Santegoets, Saskia J.A.M. Griffioen, Arjan W. Hooijberg, Erik van den Eertwegh, Alfons J.M. Thijssen, Victor L. Scheper, Rik J. Oosterhoff, Dinja de Gruijl, Tanja D. Oncoimmunology Research Paper 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(+) DCs found in the human skin to CD14(+)CD141(+) macrophage-like cells. Here, as a model of tumor-conditioned DC maturation, we functionally assessed CD14(-) and CD14(+) DCs that matured in vitro upon exposure to IL-10. IL-10-induced CD14(+) 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(+) cells infiltrating melanoma metastases. Compared with DC matured under standard conditions, CD14(+) 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(+) T-cell priming capacity and to induce proliferative T-cell anergy. In contrast to their CD14(+) counterparts, CD14(-) 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(+) DCs as compared with DCs matured in standard conditions or CD14(−) 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(+) phenotype, allowing for normal DC maturation and providing a potential means of therapeutic intervention. Landes Bioscience 2013-04-01 2013-04-01 /pmc/articles/PMC3654600/ /pubmed/23734330 http://dx.doi.org/10.4161/onci.23837 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Research Paper Lindenberg, Jelle J. van de Ven, Rieneke Lougheed, Sinéad M. Zomer, Anoek Santegoets, Saskia J.A.M. Griffioen, Arjan W. Hooijberg, Erik van den Eertwegh, Alfons J.M. Thijssen, Victor L. Scheper, Rik J. Oosterhoff, Dinja de Gruijl, Tanja D. Functional characterization of a STAT3-dependent dendritic cell-derived CD14(+) cell population arising upon IL-10-driven maturation |
title | Functional characterization of a STAT3-dependent dendritic cell-derived CD14(+) cell population arising upon IL-10-driven maturation |
title_full | Functional characterization of a STAT3-dependent dendritic cell-derived CD14(+) cell population arising upon IL-10-driven maturation |
title_fullStr | Functional characterization of a STAT3-dependent dendritic cell-derived CD14(+) cell population arising upon IL-10-driven maturation |
title_full_unstemmed | Functional characterization of a STAT3-dependent dendritic cell-derived CD14(+) cell population arising upon IL-10-driven maturation |
title_short | Functional characterization of a STAT3-dependent dendritic cell-derived CD14(+) cell population arising upon IL-10-driven maturation |
title_sort | functional characterization of a stat3-dependent dendritic cell-derived cd14(+) cell population arising upon il-10-driven maturation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654600/ https://www.ncbi.nlm.nih.gov/pubmed/23734330 http://dx.doi.org/10.4161/onci.23837 |
work_keys_str_mv | AT lindenbergjellej functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT vandevenrieneke functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT lougheedsineadm functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT zomeranoek functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT santegoetssaskiajam functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT griffioenarjanw functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT hooijbergerik functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT vandeneertweghalfonsjm functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT thijssenvictorl functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT scheperrikj functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT oosterhoffdinja functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation AT degruijltanjad functionalcharacterizationofastat3dependentdendriticcellderivedcd14cellpopulationarisinguponil10drivenmaturation |