Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE251705 | GEO | 2025/04/03
REPOSITORIES: GEO
Similar Datasets
Project description:Langerhans cells (LCs) are a unique population of phagocytes programmed within embryonic skin to maintain tissue and immunological homeostasis at the epidermal barrier site. Unique amongst tissue-resident macrophages, LCs play roles in skin innervation and repair, while also functioning as migrating professional antigen presenting cells, a capability classically assigned to dendritic cells (DC). We current lack insight into the molecular pathways that determine this dichotomy, when they are established, and whether precursors recruited to the adult skin niche access the same instructive signals laid down in utero. Tracking differentiation of monocyte-derived (m)LCs after destruction of embryo-derived cells in murine adult skin, revealed intrinsic intra-epidermal heterogeneity and selection of MDP-monocytes to by-pass gene programmes specifying a macrophage fate. Adopting a process unique to adult skin, subsequent extrinsic specification of EpCAM+ precursors via follicular Notch ligands, and aryl hydrocarbon receptor (Ahr) signalling, combined to determine commitment to resident mLCs. Using a unique human LC dataset, we demonstrated that embryo-derived (e)LCs in newborn human skin retained transcriptional evidence of their macrophage origin, which was superseded by a distinct DC-like immune modules following proliferation in infant skin. Thus, convergent differentiation of monocytes within adult skin exploits novel molecular pathways to replicate conditioning of eLC towards more immunogenic DC-like cells within post-natal skin.
2024-09-08 | GSE247878 | GEO
Project description:Langerhans cells (LCs) are a unique population of phagocytes programmed within embryonic skin to maintain tissue and immunological homeostasis at the epidermal barrier site. Unique amongst tissue-resident macrophages, LCs play roles in skin innervation and repair, while also functioning as migrating professional antigen presenting cells, a capability classically assigned to dendritic cells (DC). We current lack insight into the molecular pathways that determine this dichotomy, when they are established, and whether precursors recruited to the adult skin niche access the same instructive signals laid down in utero. Tracking differentiation of monocyte-derived (m)LCs after destruction of embryo-derived cells in murine adult skin, revealed intrinsic intra-epidermal heterogeneity and selection of MDP-monocytes to by-pass gene programmes specifying a macrophage fate. Adopting a process unique to adult skin, subsequent extrinsic specification of EpCAM+ precursors via follicular Notch ligands, and aryl hydrocarbon receptor (Ahr) signalling, combined to determine commitment to resident mLCs. Using a unique human LC dataset, we demonstrated that embryo-derived (e)LCs in newborn human skin retained transcriptional evidence of their macrophage origin, which was superseded by a distinct DC-like immune modules following proliferation in infant skin. Thus, convergent differentiation of monocytes within adult skin exploits novel molecular pathways to replicate conditioning of eLC towards more immunogenic DC-like cells within post-natal skin.
2024-09-08 | GSE247874 | GEO
Project description:It is still debated whether the homeostatic function of tissue macrophages is dependent on their origin, and evidence suggests this may depend on the tissue of macrophage residence. Here, we answered this question for Langerhans cells (LCs), an embryonic-derived mononuclear phagocyte that has features of both tissue macrophages and dendritic cells. Using time-course analyses, bone marrow chimeras and fate tracing models, we found that the complete elimination of embryonic-derived LCs at steady state results in their repopulation from circulating monocytes. However, monocyte-derived LCs inefficiently replenished the epidermal niche. Instead, these cells preferentially migrated to skin draining lymph nodes. Mechanistically, we show that the superior migratory capability of monocyte-derived LCs is associated with higher expression of CD207/Langerin, a C-type lectin involved in the capture of skin microbes. Our data shows that ontogeny plays a role in the migratory behavior of epidermal LCs.
2024-10-31 | GSE261079 | GEO
Project description:Many studies have shown that the mucous membranes and skin are at the interface with different external environments and face the disparity of pathogenic effects, such as biological agents, chemical or physical environment. This difference may demand distinct immune responses. However, the mechanism to induce the distinct immune responses in mucous and skin is largely unknown. Dendritic cells of mucosa and skin are crucial in the initiation of immune responses, maintenance of self-tolerance and antigens presentation T cells. The different functions between mucosal and epidermal dendritic cells may play an important role in different immune responses. To compare the different gene expression of the mucosal DC and Langerhans cells (LC), we utilized microarrays to investigate different gene expression profiles in mucosal DC isolated from PPs (PDC) and epidermal LC from skin (ELC). 3548 genes were shown to be differentially expressed between PDC and ELC. According to genes annotations, 105 genes may be involved in immunity process. The genes involved in immune process were categorized to five groups related to DC function, including antigen presentation, antigen uptake, cytokines chemokines, and receptors, cell surface molecules and signal transduction. 11 of the highest expressed genes were selected as the candidate genes and reformed by real-time PCR. These 11 selected genes might be suitable candidates to further study the difference of gene expression between mucosal DC and epidermal LC and would be used for design for new vaccine. Beads and FACS sort were used to isolate dendritic cells from Peyer's patches and epidermal of skin from 80 four-week-old female BALB/c mice. Dendritic cells from Peyer's patches were pooled as one sample, and dendritic cells from epidermal of skin were pooled as another sample. RNA isolation, amplification, cDNA labelling, microarray hybridization and analyses were performed according to the Affymetrix manual book.
2009-04-28 | E-GEOD-15754 | biostudies-arrayexpress
Project description:Many studies have shown that the mucous membranes and skin are at the interface with different external environments and face the disparity of pathogenic effects, such as biological agents, chemical or physical environment. This difference may demand distinct immune responses. However, the mechanism to induce the distinct immune responses in mucous and skin is largely unknown. Dendritic cells of mucosa and skin are crucial in the initiation of immune responses, maintenance of self-tolerance and antigens presentation T cells. The different functions between mucosal and epidermal dendritic cells may play an important role in different immune responses. To compare the different gene expression of the mucosal DC and Langerhans cells (LC), we utilized microarrays to investigate different gene expression profiles in mucosal DC isolated from PPs (PDC) and epidermal LC from skin (ELC). 3548 genes were shown to be differentially expressed between PDC and ELC. According to genes annotations, 105 genes may be involved in immunity process. The genes involved in immune process were categorized to five groups related to DC function, including antigen presentation, antigen uptake, cytokines chemokines, and receptors, cell surface molecules and signal transduction. 11 of the highest expressed genes were selected as the candidate genes and reformed by real-time PCR. These 11 selected genes might be suitable candidates to further study the difference of gene expression between mucosal DC and epidermal LC and would be used for design for new vaccine.
2009-04-28 | GSE15754 | GEO
Project description:miRNA profiling of CD34+ derived, in vitro-generated Langerhans cells (LCs) and interstitial-type dendritic cells (intDCs). Epidermal Langerhans cells (LCs) form a network of dendritic cells (DCs) in basal/suprabasal layers of the skin and are characterized by a unique phenotype (CD207+ CD1abright CD324+ CD11b-). Due to their specific location at body surfaces, LCs are constantly exposed to environmental stimuli. Conversely, interstitial-type DCs (intDCs) are located in adjacent tissues and can be discriminated from LCs phenotypically (CD207- CD1adim CD324- CD11b+). These DCs constitute a second line of defense against pathogens that have crossed the epithelial barrier. During development both DC subsets originally arise from myeloid progenitor cells via monocyte-committed intermediates in response to specific microenvironmental signals. Additionally certain pools of DCs can be replenished by tissue resident cells or monocytes in response to specific microenvironmental signals (2, 4, 5). In vitro generated GM-CSF/IL-4-dependent DCs derived either from CD14+ monocytes or via CD14+CD11b+ monocyte intermediates from CD34+ progenitor cells share many characteristics with intDCs in vivo. On the other hand, LCs generated from CD34+ cells under serum-free TGF-beta1-dependent conditions phenotypically resemble epidermal-resident LCs. Since these two DC subsets are of considerable interest for clinical cell therapy studies, an improved understanding of their development and function is of substantial relevance. To identify differentially expressed miRNAs in DC subsets, we performed a miRNA screen. Therefore, we generated LCs or intDCs from human CD34+ cord blood haematopoietic progenitor cells as described. For intDCs, CD34+ cells (1 x 104 to 2 x 104/ml per well) were cultured in 24-well tissue culture plates in serum free CellGro® DC medium (CellGenix, Freiburg, Germany) supplemented with GM-CSF (100 ng/ml), SCF (20 ng/ml), FL (50 ng/ml) and TNFalpha (2.5 ng/ml) for 3-5 days and subsequently with GM-CSF (100 ng/ml) and IL-4 (2.5 ng/ml) for 4-5 days. For LCs, CD34+ cells (1 x 104 to 2 x 104/ml per well) were cultured in 24-well tissue culture plates in serum free CellGro® DC medium (CellGenix, Freiburg, Germany) supplemented with GM-CSF (100 ng/ml), SCF (20 ng/ml), FL (50 ng/ml), TNFalpha (2.5 ng/ml) and TGF-beta1 (0.5 ng/ml). The well-established immunophenotype of LCs (CD1ahi CD11b- CD207+ CD324+) and intDCs (CD1a+ CD11b+ CD207- CD324-) was confirmed by FACS. These two DC subsets were purified and submitted to differential miRNA profiling. Two conditioned experiment LCs vs. intDCs. Biological replicates: 3 LCs, 3 intDCs, independently differentiated, harvested and purified. 3 replicates each were pooled and hybridized on one array. Supplementary files linked below.
2010-06-24 | E-GEOD-20215 | biostudies-arrayexpress
Project description:TGF-β family ligands are key regulators of dendritic cell (DC) differentiation and activation. Epidermal Langerhans cells (LCs) require TGF-β family signaling for their differentiation and canonical TGF-β1 signaling secures a non-activated LC state. LCs reportedly control skin inflammation and are replenished from peripheral blood monocytes, which also give rise to pro-inflammatory monocyte-derived DCs (moDCs). By studying mechanisms in inflammation, we previously screened LCs vs moDCs for differentially expressed miRNAs. miR-424/503 was the most strongly inversely regulated (moDCs > LCs). We found that miR-424/503 is induced during moDC differentiation and promotes moDC differentiation in human and mouse. Inversely, forced repression of miR-424 during moDC differentiation facilitated TGF-β1-dependent LC differentiation. Mechanistically, miR-424/503 deficiency in monocyte/DC precursors leads to the induction of TGF-β1-response genes critical for LC differentiation. Therefore, the miR-424/503 gene cluster plays a decisive role in anti-inflammatory LC vs pro-inflammatory moDC differentiation from monocytes.
2021-03-27 | GSE169717 | GEO
Project description:Characterization of functionally distinct Dendritic Cell (DC) subsets in mice has fueled interest in whether analogous counterparts exist in humans. Transcriptional modules of coordinately expressed genes were utilized for defining shared functions between the species. Comparing modules derived for four human skin DC subsets, and modules derived from the Immunological Genome Project database for all mouse DC subsets, revealed that human Langerhans Cells (LCs) and the mouse XCR1+CD8α+CD103+ DCs shared the Class I-mediated antigen processing and cross-presentation transcriptional modules that, however, were not seen in mouse LCs. Furthermore, human LCs were enriched in a transcriptional signature specific to the blood cross-presenting CD141/BDCA-3+ DCs, the proposed equivalent to mouse CD8α+ DCs. Consistent with our analysis, LCs were highly adept at inducing primary CTL responses. Thus, our study suggests that the function of LCs may not be conserved between mouse and human and supports human LCs as an especially relevant therapeutic target. RNA from sorted populations was purified using TRIzol. RNA was processed, amplified, labeled and hybridized at Washington University Core Facility (GTAC) with Illumina HumanHT-12 v4 Expression BeadChip. Data were background subtracted and quantile normalized.
2015-03-27 | E-GEOD-66355 | biostudies-arrayexpress
Project description:DC, monocyte and macrophage networks are evolutionarily conserved but the distinct subsets have been difficult to distinguish due to shared overlapping phenotypic markers between the cells. Using transcriptome microarray profiling of human and mouse mononuclear phagocyte subsets, we have distinguished human dermal DCs from monocyte-derived cells and macrophages. Gene Expression from total RNA from human dermal macrophages, epidermal LCs and CD14+ cells subsets purified by FACS
2014-10-15 | E-GEOD-60317 | biostudies-arrayexpress
Project description:Characterization of functionally distinct Dendritic Cell (DC) subsets in mice has fueled interest in whether analogous counterparts exist in humans. Transcriptional modules of coordinately expressed genes were utilized for defining shared functions between the species. Comparing modules derived for four human skin DC subsets, and modules derived from the Immunological Genome Project database for all mouse DC subsets, revealed that human Langerhans Cells (LCs) and the mouse XCR1+CD8α+CD103+ DCs shared the Class I-mediated antigen processing and cross-presentation transcriptional modules that, however, were not seen in mouse LCs. Furthermore, human LCs were enriched in a transcriptional signature specific to the blood cross-presenting CD141/BDCA-3+ DCs, the proposed equivalent to mouse CD8α+ DCs. Consistent with our analysis, LCs were highly adept at inducing primary CTL responses. Thus, our study suggests that the function of LCs may not be conserved between mouse and human and supports human LCs as an especially relevant therapeutic target.
2015-03-27 | GSE66355 | GEO