Similar Datasets
Project description:Tolerogenic dendritic cells (DCs) are key players in maintaining immunological homeostasis, dampening immune responses, and promoting tolerance. DC-10, a tolerogenic population of human IL-10-producing DCs 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 markers that uniquely identify DC-10 has limited in vivo studies. By in vitro gene expression profiling of differentiated human DCs, we identified CD141 and CD163 as surface markers for DC-10. The coexpression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of DC-10 from the peripheral blood. CD14+CD16+CD141+CD163+ cells isolated from the peripheral blood of healthy subjects (ex vivo DC-10) produced spontaneously and upon activation of IL-10 and limited levels of IL-12. Moreover, in vitro stimulation of allogeneic naive CD4+ T cells with ex vivo DC-10 induced the differentiation of alloantigen-specific CD49b+LAG-3+ Tr1 cells. Finally, ex vivo DC-10 and in vitro generated DC-10 exhibited a similar transcriptional profile, which are characterized by an anti-inflammatory and pro-tolerogenic signature. These results provide new insights into the phenotype and molecular signature of DC-10 and highlight the tolerogenic properties of circulating DC-10. These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.
| S-EPMC6952411 | biostudies-literature
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
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 | GSE117945 | GEO
Project description:Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10)
| PRJNA483777 | ENA
Project description:Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10) [expression array]
| PRJNA483779 | ENA
Project description:Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10) [RNA-seq]
| PRJNA483780 | ENA
Project description:To identify factors associated with the immunosuppressor activity of IL-10+ DC, these cells were obtained from VertX mice immunized with OVA+imiquimod and compared with IL-10- DCs from the same mice and from VertX mice, either untreated or vaccinated with OVA+poly(I:C).
2022-11-02 | GSE198973 | GEO
Project description:Gene expression profiling dendritic cells (DC) producing IL-10
| PRJNA817602 | ENA
Project description:Two subsets of conventional dendritic cells (cDCs) with distinct cell surface markers and functions exist in mouse and human. The two subsets of cDCs are specialized antigen-presenting cells that initiate T cell immunity and tolerance. In the mouse, a migratory cDC precursor (pre-CDC) originates from defined progenitors in the bone marrow (BM). Small numbers of short-lived pre-CDCs travel through the blood and replace cDCs in the peripheral organs, maintaining homeostasis of the highly dynamic cDC pool. However, the identity and distribution of the immediate precursor to human cDCs has not been defined. Using a tissue culture system that supports the development of human DCs, we identify a migratory precursor (hpre-CDC) that exists in human cord blood, BM, blood, and peripheral lymphoid organs. hpre-CDCs differ from premonocytes that are restricted to the BM. In contrast to earlier progenitors with greater developmental potential, the hpre-CDC is restricted to producing CD1c(+) and CD141(+) Clec9a(+) cDCs. Studies in human volunteers demonstrate that hpre-CDCs are a dynamic population that increases in response to levels of circulating Flt3L.
| S-EPMC4354370 | biostudies-literature
Project description:Infection by Listeria monocytogenes (Lm) causes serious sepsis and meningitis leading to mortality in neonates. This work explored the ability of CD11c(high) lineage DCs to induce CD8+ T-cell immune protection against Lm in mice before 7 days of life, a period symbolized by the absence of murine IL-12p70-producing CD11c(high)CD8α+ dendritic cells (DCs). We characterized a dominant functional Batf3-dependent precursor of CD11c(high) DCs that is Clec9A+CD205+CD24+ but CD8α- at 3 days of life. After Lm-OVA infection, these pre-DCs that cross-present Ag display the unique ability to produce high levels of IL-12p40 (not IL-12p70 nor IL-23), which enhances OVA-specific CD8+ T cell response, and regulatory IL-10 that limits OVA-specific CD8+ T cell response. Targeting these neonatal pre-DCs for the first time with a single treatment of anti-Clec9A-OVA antibody in combination with a DC activating agent such as poly(I:C) increased the protection against later exposure to the Lm-OVA strain. Poly(I:C) was shown to induce IL-12p40 production, but not IL-10 by neonatal pre-DCs. In conclusion, we identified a new biologically active precursor of Clec9A+ CD8α- DCs, endowed with regulatory properties in early life that represents a valuable target to augment memory responses to vaccines.
| S-EPMC4830566 | biostudies-literature