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Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10) [RNA-seq]

ABSTRACT: Tolerogenic dendritic cells (DC) are key players in maintaining immunological homeostasis, dampening immune reactions, and promoting tolerance. DC-10, a tolerogenic population of human IL-10-producing DC characterized by the expression of HLA-G and ILT4, play a pivotal role in promoting tolerance via T regulatory type 1 (Tr1) cells. Thus far, the absence of specific biomarkers that uniquely identify DC-10 limited their studies in vivo. By gene expression profiling of in vitro differentiated human DC, we identified CD141 and CD163 as specific surface markers for DC-10. The co-expression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of blood circulating DC-10. FACS-isolated CD14+CD16+CD141+CD163+ cells (ex vivo DC-10) from peripheral blood of healthy subjects produced spontaneously and upon activation IL-10 and limited levels of IL-12. Moreover, in vitro stimulation of allogeneic naive CD4+ T cells with ex vivo isolated CD14+CD16+CD141+CD163+ cells induced the differentiation of allo-specific Tr1 cells. Finally, ex vivo isolated CD14+CD16+CD141+CD163+ cells and in vitro differentiated DC-10 exhibited a similar transcriptional profile, characterized by anti-inflammatory and pro-tolerogenic signature. These results provide new insight into the DC-10 phenotype and on the role of circulating DC-10 in modulating T cell responses and promoting Tr1 cells. These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117945 | GEO | 2019/06/07

REPOSITORIES: GEO

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Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10) [expression array]

Project description:Tolerogenic dendritic cells (DC) are key players in maintaining immunological homeostasis, dampening immune reactions, and promoting tolerance. DC-10, a tolerogenic population of human IL-10-producing DC characterized by the expression of HLA-G and ILT4, play a pivotal role in promoting tolerance via T regulatory type 1 (Tr1) cells. Thus far, the absence of specific biomarkers that uniquely identify DC-10 limited their studies in vivo. By gene expression profiling of in vitro differentiated human DC, we identified CD141 and CD163 as specific surface markers for DC-10. The co-expression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of blood circulating DC-10. FACS-isolated CD14+CD16+CD141+CD163+ cells (ex vivo DC-10) from peripheral blood of healthy subjects produced spontaneously and upon activation IL-10 and limited levels of IL-12. Moreover, in vitro stimulation of allogeneic naive CD4+ T cells with ex vivo isolated CD14+CD16+CD141+CD163+ cells induced the differentiation of allo-specific Tr1 cells. Finally, ex vivo isolated CD14+CD16+CD141+CD163+ cells and in vitro differentiated DC-10 exhibited a similar transcriptional profile, characterized by anti-inflammatory and pro-tolerogenic signature. These results provide new insight into the DC-10 phenotype and on the role of circulating DC-10 in modulating T cell responses and promoting Tr1 cells. These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.

2019-06-07 | GSE117946 | GEO

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Gene array analysis of human adult skin and spleen antigen presenting cells.

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Human inflammatory dendritic cells induce Th17 differentiation

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Project description:The human immune system evolves gradually from the embryo to adult, continuously adapting to the ever-changing environment of the human body. The ability of our immune system to sense external cues and adapt as we develop is as important in the early tolerogenic environment of the fetus, as it is in the constantly pathogen-challenged adult. Dendritic cells (DC), professional antigen sensing and presenting cells, play a crucial role in such processes as sentinels of the immune system, initiating and regulating immune responses. We have previously characterised CD14+ DC, CD1c+DC and CD141+DC subset by flow cytometry and microarray transcriptome analysis in adult mucosal tissues, and have described their superior abilities to either induce IL-17 responses or to cross-present external antigens respectively. However, the role of such DC subsets in the tolerogenic environment of the fetus remains undefined, prompting us to investigate the ontogeny and functional significance of human fetal DCs.

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Tolerogenic Dendritic Cells Engineered with IL-10 and Antigen Control Pathogenic T Cell Responses and Promote Type 1 T Regulatory Cells

Project description:Dendritic cells (DC) play a critical role in the maintenance of tissue homeostasis and in promoting tolerance, thus acting as regulatory cells. Tolerogenic DC (tolDC) represent the cells of choice to fulfill the goal of restoring antigen (Ag)-specific tolerance since they can dampen Ag-specific T cell responses, induce pathogenic T cell exhaustion, and Ag-specific regulatory T cells. Here we efficiently generate tolDC by genetic engineering of monocytes with bidirectional lentiviral vectors co-encoding for immunodominant Ag-derived peptides (Ovalbumin or Matrix Protein 1, Insulin and Gliadin) in combination with IL-10 (DCIL-10/Ag). DCIL-10/Ag secrete high amounts of IL_x0002_10 in the absence of pro-inflammatory cytokines and efficiently modulate Ag-specific CD4+ and CD8+ T cell activation and proliferation in vitro in healthy subjects and Celiac Disease patients. DCIL-10/Ag promote Ag-specific CD49b+LAG-3 + T cells, which display the type 1 T regulatory (Tr1) cell gene signature in vitro. In vivo administration of DCIL-10/Ag promote Ag-specific Tr1 cells and prevent type 1 diabetes development in two murine models of disease. In conclusion, we generate an innovative approach based on the use of autologous engineered DC, which effectively modulate pathogenic CD4+ and CD8+ T cell responses in vitro and in vivo by promoting Ag_x0002_specific Tr1 cells suitable for cell-based therapy for restoring tolerance in T cell mediated diseases

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Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10)

Project description:Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10)

| PRJNA483777 | ENA

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