Transcriptomics profiling of CD141+ dendritic cells isolated from peripheral blood or synovial fluid of arthritis patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE108174 | GEO | 2018/12/15
REPOSITORIES: GEO
Similar Datasets
Project description:Total RNA sequencing was performed on CD141+ DC isloated from peripheral blood of healthy individuals (n=5) or synovial fluid of patients with inflammatory arthritis (n=6)
2020-05-15 | GSE98950 | GEO
Project description:Human immune cell subsets develop in immunodeficient mice following reconstitution with human CD34+ haematopoietic stem cells. These “humanized” mice are useful models to study human immunology and human-tropic infections, autoimmunity and cancer. However, some human immune cell subsets are unable to fully develop or acquire full functional capacity due to a lack of cross-reactivity of many growth factors and cytokines between species. “Classical” (c) DC arise from a separate precursor to monocytes and initiate and direct T cell responses. In mice they can be further categorized into cDC1, which mediate Th1 and CD8+ T cell responses, and cDC2, which mediate Th2 and Th17 responses. The gene expression profiles and phenotype human CD141+ DC and CD1c+ DC subsets align with mouse cDC1 and cDC2 respectively but there are also key interspecies differences. Human CD141+ DC and CD1c+ DC develop in humanized mice but the extent to which they resemble their human blood counterparts is not yet known. We therefore analyzed the gene expression profiles of CD141+ DC and CD1c+ DC in humanized mice and demonstrated that they closely resemble those in human blood, making this an attractive model in which to study human DC in vitro or on vivo. We further used this model to explore changes in DC subsets after activation with TLR3 and TLR7/8 ligands, poly I:C and R848 in vivo. A core panel of genes consistent with DC maturation status were upregulated by both subsets. R848 specifically upregulated genes associated with Th17 responses by CD1c+ DC, whilst poly I:C upregulated IFN-λ genes specifically by CD141+ DC. Thus CD141+ DC and CD1c+ DC share a similar activation profiles in vivo but also have induce unique signatures that support specialized roles in CD8+ T cell priming and Th17 responses respectively. '
2017-09-22 | GSE99666 | GEO
Project description:Antigen presenting cells (APC) are a heterogenous population, comprised of macrophages/monocytes (CD14+ cells), classical dendritic cells (CD141+DC and CD1c+ DC) and pDC. Upon stimulation, APC migrate from peripheral organs to lymph nodes, where they drive T cell specific lineage fate, that is towards immune activation or suppression. APC in human tissues remain poorly defined. Through our previous published data we have charactised APC within adult skin and blood. Here we extend these findings, by performing microarray analysis of adult lung CD14+ DC, CD141+ DC and CD1c+ DC. Once, we were confident we could clearly distinguish the populations of interest (CD14+ cell, CD141+ DC and CD1c+ DC) from other cells, we sorted FACS purified the cells and prepared them for gene array analysis.
2016-12-19 | GSE87494 | 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: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:Antigen presenting cells (APC) are a heterogenous population, comprised of macrophages/monocytes (CD14+ cells), classical dendritic cells (CD141+DC and CD1c+ DC) and pDC. Upon stimulation, APC migrate from peripheral organs to lymph nodes, where they drive T cell specific lineage fate, that is towards immune activation or suppression. APC in human tissues remain poorly defined. Through our previous published data we have charactised APC within adult skin and blood. Here we extend these findings, by increasing the sample for skin CD14+ DC and CD1c+ DC and performing gene array analysis of adult spleen CD14+ DC, CD141+DC and CD1c+ DC. Once, we were confident we could clearly distinguish our populations (CD14+ cell, CD141+ DC and CD1c+ DC) of interest from other cells, we sorted FACS purified the cells and prepared them for gene array analysis. Through generating subset specific gene signatures and comparing CMAP scores we confirmed we had identified equivalent APC subsets across human adult skin and spleen.
2016-12-19 | GSE85305 | GEO
Project description:In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-?1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells. Total RNA were isolated from purified human CD1c+ (BDCA1+) and CD141+ (BDCA3+) mDCs sorted from different tissues, including human blood, spleen and lungs of humanized mice, and human lungs. Eighteen samples in total were analyzed from different donors and tissues.
2013-04-04 | E-GEOD-43184 | biostudies-arrayexpress
Project description:The human bone marrow (BM) gives rise to all distinct blood cell lineages, including CD1c+ and CD141+ myeloid dendritic cells (DC) and monocytes. These cell subsets are also present in peripheral blood (PB) and lymphoid tissues. However, the difference between the BM and PB compartment in terms of differentiation state and immunological role of DC is not yet known. The BM may represent both a site for development as well as a possible effector site and so far, little is known in this light with respect to different DC subsets. Using genome-wide transcriptional profiling we found clear differences between the BM and PB compartment and a location-dependent clustering for CD1c+ and CD141+ was demonstrated. DC subsets from BM clustered together and separate from the corresponding subsets from PB, which similarly formed a cluster. In BM, a common proliferating and immature differentiating state was observed for the two DC subsets, whereas DC from the PB showed a more immune-activated mature profile. In contrast, BM-derived slan+ non-classical monocytes were closely related to their PB counterparts and not to DC subsets, implying a homogenous prolife irrespective of anatomical localization. Additional functional tests confirmed these transcriptional findings. DC-like functions were prominently exhibited by PB DC. They surpassed BM DC in maturation capacity, cytokine production and induction of CD4+ and CD8+ T cell proliferation. This first study on myeloid DC in healthy human BM offers new information on steady-state DC biology and could potentially serve as a starting point for further research on these immune cells in healthy conditions as well as in diseases.
2018-12-21 | GSE112770 | GEO
Project description:Expression data from LCH lesion subpopulations and healthy donors' peripheral blood specimens Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder that is characterized by the inflammatory lesions with pathogenic CD1a+CD207+ dendritic cells (DCs). BRAFV600E and other somatic activating MAPK gene mutations have been identified in differentiating bone marrow and blood myeloid cells, but the origin of the LCH lesion CD1a+CD207+DCs and mechanisms of lesion formation remain incompletely defined. In order to identify candidate LCH CD1a+CD207+DCs’ precursor populations, gene expression profiles of LCH lesion CD1a+CD207+DCs were first compared to established gene signatures from human myeloid cell subpopulations. Interestingly, the CD1c+ myeloid DC (mDC) gene signature was most enriched in the LCH CD1a+CD207+DC’ transcriptome. Additionally, the BRAFV600E allele was not only localized to CD1a+CD207-DCs and CD1a+CD207+DCs, but it was also identified in CD1c+mDCs in LCH lesions. Transcriptomes of CD1a+CD207-DCs were nearly indistinguishable from CD1a+CD207+DCs (both CD207low and CD207high subpopulations). Transcription profiles of LCH lesion CD1a+CD207+DCs and peripheral blood CD1c+mDCs from healthy donors were compared to identify potential LCH DC-specific biomarkers. HLADQB2 expression was significantly increased in LCH lesion CD1a+CD207+DCs compared to circulating CD1c+mDCs from healthy donors, and HLA-DQB2 antigen was identified on LCH lesion CD1a+CD207- and CD1a+CD207+DCs as well as on CD1c+(CD1a+CD207-) mDCs, but not in any other lesion myeloid subpopulations. Interestingly, HLADQB2 expression was specific to peripheral blood of patients with BRAFV600E+ peripheral blood mononuclear cells (PBMC), and HLA-DQB2+CD1c+blood cells were highly enriched for the BRAFV600E in these patients. These data support a model where blood CD1c+mDCs with activated ERK migrate to lesion sites where they differentiate into pathogenic CD1a+CD207+ DCs.
2020-01-21 | GSE122674 | GEO
Project description:Expression data from LCH lesion subpopulations and healthy donors' peripheral blood specimens Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder that is characterized by the inflammatory lesions with pathogenic CD1a+CD207+ dendritic cells (DCs). BRAFV600E and other somatic activating MAPK gene mutations have been identified in differentiating bone marrow and blood myeloid cells, but the origin of the LCH lesion CD1a+CD207+DCs and mechanisms of lesion formation remain incompletely defined. In order to identify candidate LCH CD1a+CD207+DCs’ precursor populations, gene expression profiles of LCH lesion CD1a+CD207+DCs were first compared to established gene signatures from human myeloid cell subpopulations. Interestingly, the CD1c+ myeloid DC (mDC) gene signature was most enriched in the LCH CD1a+CD207+DC’ transcriptome. Additionally, the BRAFV600E allele was not only localized to CD1a+CD207-DCs and CD1a+CD207+DCs, but it was also identified in CD1c+mDCs in LCH lesions. Transcriptomes of CD1a+CD207-DCs were nearly indistinguishable from CD1a+CD207+DCs (both CD207low and CD207high subpopulations). Transcription profiles of LCH lesion CD1a+CD207+DCs and peripheral blood CD1c+mDCs from healthy donors were compared to identify potential LCH DC-specific biomarkers. HLADQB2 expression was significantly increased in LCH lesion CD1a+CD207+DCs compared to circulating CD1c+mDCs from healthy donors, and HLA-DQB2 antigen was identified on LCH lesion CD1a+CD207- and CD1a+CD207+DCs as well as on CD1c+(CD1a+CD207-) mDCs, but not in any other lesion myeloid subpopulations. Interestingly, HLADQB2 expression was specific to peripheral blood of patients with BRAFV600E+ peripheral blood mononuclear cells (PBMC), and HLA-DQB2+CD1c+blood cells were highly enriched for the BRAFV600E in these patients. These data support a model where blood CD1c+mDCs with activated ERK migrate to lesion sites where they differentiate into pathogenic CD1a+CD207+ DCs.
2020-01-21 | GSE122476 | GEO