Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal T cells via TGF-β
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE43184 | GEO | 2013/04/04
SECONDARY ACCESSION(S): PRJNA184857
REPOSITORIES: GEO
Similar Datasets
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:Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs. Gene expression analysis using total RNA from specific human and mouse monocyte and dendritic cell subsets purified by FACS.
2012-07-11 | E-GEOD-35457 | biostudies-arrayexpress
Project description:Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs. Gene expression analysis using total RNA from specific human and mouse monocyte and dendritic cell subsets purified by FACS.
2012-07-11 | E-GEOD-35458 | biostudies-arrayexpress
Project description:Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs.
2012-07-12 | GSE35458 | GEO
Project description:Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs.
2012-07-12 | GSE35457 | GEO
Project description:Innate sensing of viruses by dendritic cells (DCs) is critical for the initiation of anti-viral adaptive immune responses. Virus, however, have evolved to suppress immune activation in infected cells. We now analyze the susceptibility of different populations of dendritic cells to viral infections. We find that circulating human CD1c+ DCs support infection by HIV and influenza virus. Viral infection of CD1c+ DCs is essential for virus-specific CD8+ T cell activation and cytosolic sensing of the virus. In contrast, circulating human CD141+ DCs and pDCs constitutively limit viral fusion. The small GTPase RAB15 mediates this differential viral resistance in DC subsets through selective expression in CD141+ DCs and pDCs. Therefore, dendritic cell sub-populations evolved constitutive resistance mechanisms to mitigate viral infection during induction of antiviral immune response.
2017-05-22 | GSE76511 | 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:Dendritic cells (DC) are antigen presenting cells controlling T cell activation. In human, the diversity, ontogeny and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88-CD1c+CD163+ DC (termed as DC3) as an immediate precursor of inflammatory CD88-CD14+CD1c+CD163+FcεRI+ DC. DC3 develop via a specific pathway, independent from the cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors, and are activated by GM-CSF. As classical DC, but unlike monocytes, DC3 drove the activation of naïve T cells. In vitro, DC3 displayed a distinctive ability to prime CD8+ T cells expressing a tissue-homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor-b (TGF-β) signaling. In vivo, DC3 infiltrated luminal breast cancer primary tumors and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Altogether, these findings define DC3 as a lineage of inflammatory DC endowed with a strong potential to regulate tumor immunity.
2020-05-23 | GSE151087 | GEO
Project description:Dendritic cells (DC) are antigen presenting cells controlling T cell activation. In human, the diversity, ontogeny and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88-CD1c+CD163+ DC (termed as DC3) as an immediate precursor of inflammatory CD88-CD14+CD1c+CD163+FcεRI+ DC. DC3 develop via a specific pathway activated by GM-CSF, independent from the cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. As classical DC, but unlike monocytes, DC3 drove the activation of naïve T cells. In vitro, DC3 displayed a distinctive ability to prime CD8+ T cells expressing a tissue-homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor-b (TGF-β) signaling. In vivo, DC3 infiltrated luminal breast cancer primary tumors and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Altogether, these findings define DC3 as a lineage of inflammatory DC endowed with a strong potential to regulate tumor immunity.
2020-05-23 | GSE151072 | 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