Unknown

Dataset Information

0

Functional characterization of a STAT3-dependent dendritic cell-derived CD14+ cell population arising upon IL-10-driven maturation.


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+ 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.

SUBMITTER: Lindenberg JJ 

PROVIDER: S-EPMC3654600 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Functional characterization of a STAT3-dependent dendritic cell-derived CD14<sup>+</sup> cell population arising upon IL-10-driven maturation.

Lindenberg Jelle J JJ   van de Ven Rieneke R   Lougheed Sinéad M SM   Zomer Anoek A   Zomer Anoek A   Santegoets Saskia J A M SJ   Griffioen Arjan W AW   Hooijberg Erik E   van den Eertwegh Alfons J M AJ   Thijssen Victor L VL   Scheper Rik J RJ   Oosterhoff Dinja D   de Gruijl Tanja D TD  

Oncoimmunology 20130401 4


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<sup>+</sup> DCs found in the human skin to CD14<sup>+</sup>CD141<sup>+</sup> macrophage-like cells. Here, as a model of tumor-conditioned DC maturation, we functionally assessed CD14<sup>-</sup> and CD14<sup>+</sup> DCs that matured in vitro upon exposure to  ...[more]

Similar Datasets

| S-EPMC1325006 | biostudies-literature
| S-EPMC10252493 | biostudies-literature
| S-EPMC6736993 | biostudies-literature
| S-EPMC3954539 | biostudies-literature
| S-EPMC8005643 | biostudies-literature
| S-EPMC5652747 | biostudies-literature
| S-EPMC4830566 | biostudies-literature
| S-EPMC6341182 | biostudies-literature
| S-EPMC3937791 | biostudies-other
| S-EPMC6441038 | biostudies-literature