Transcriptional Profiling Uncovers Human Hyalocytes as a Unique Innate Immune Cell Population
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA615895 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Purpose: To decipher the transcriptional signature of macrophages of the human vitreous, also known as hyalocytes, and compare it to the profiles of other myeloid cell populations including human blood-derived monocytes, macrophages and brain microglia. Methods: This study involves a total of 13 patients with disorders of the vitreoretinal interface undergoing vitrectomy at the University Eye Hospital Freiburg between 2018 and 2019. Vitreal hyalocytes were characterized by fluorescence-activated cell sorting (FACS) and isolated as CD45+CD11b+CX3CR1+Mat-Mac+ cells using a FACS-based sorting protocol. RNA extraction, library preparation and RNA sequencing were performed and the sequencing data was analyzed using the Galaxy web platform. The human hyalocyte transcriptome was compared to the transcriptional profile of human macrophages, brain microglia and blood-derived monocytes obtained from public databases. Protein validation for selected factors was performed by immunohistochemistry on paraffin sections from three human donor eyes. Results: On average, 383 ± 233 hyalocytes were isolated per patient, resulting in 128 pg/µl ± 76 pg/µl total RNA per sample. RNA sequencing revealed SPP1, FTL and CD74 as the most abundantly expressed genes in hyalocytes, which was confirmed by immunofluorescence. Gene ontology (GO) enrichment analysis showed that biological processes such as “humoral immune response”, “leukocyte migration” and “antigen processing and presentation of peptide antigen” (adjusted p < 0.001) are dominating in vitreal hyalocytes. While the comparison of the gene expression profiles of hyalocytes and other myeloid cell populations, such as brain microglia or blood-derived monocytes, showed an overall strong similarity (R2 > 0.637, p < 0.001), hyalocytes revealed significant differences with respect to common leukocyte-associated factors. In particular, transcripts involved in the immune privilege of the eye, such as POMC, CD46 and CD86, were significantly increased in hyalocytes compared to other myeloid cell subsets. Conclusion: Human hyalocytes represent a unique and distinct innate immune cell population specialized and adapted for the tissue-specific needs in the human vitreous. Vitreal hyalocytes are characterized by a strong expression of genes related to antigen processing and presentation as well as immune modulation. Thus, hyalocytes may represent a clearly underestimated mediator in vitreoretinal disease and for the immune privilege of the eye.
2020-10-05 | GSE147657 | GEO
Project description:Purpose:To decipher the transcriptional signature of macrophages of the human vitreous, also known as hyalocytes, and compare it to the profiles of other myeloid cell populations including human blood-derived monocytes, macrophages, and brain microglia. Methods:This study involves a total of 13 patients of advanced age with disorders of the vitreoretinal interface undergoing vitrectomy at the University Eye Hospital Freiburg between 2018 and 2019. Vitreal hyalocytes were analyzed by fluorescence-activated cell sorting (FACS) and isolated as CD45+CD11b+CX3CR1+Mat-Mac+ cells using a FACS-based sorting protocol. RNA extraction, library preparation and RNA sequencing were performed and the sequencing data was analyzed using the Galaxy web platform. The transcriptome of human hyalocytes was compared to the transcriptional profile of human blood-derived monocytes, macrophages and brain microglia obtained from public databases. Protein validation for selected factors was performed by immunohistochemistry on paraffin sections from three human donor eyes. Results:On average, 383 ± 233 hyalocytes were isolated per patient, resulting in 128 pg/?l ± 76 pg/?l total RNA per sample. RNA sequencing revealed that SPP1, FTL, CD74, and HLA-DRA are among the most abundantly expressed genes in hyalocytes, which was confirmed by immunofluorescence for CD74, FTL, and HLA-DRA. Gene ontology (GO) enrichment analysis showed that biological processes such as "humoral immune response," "leukocyte migration," and "antigen processing and presentation of peptide antigen" (adjusted p < 0.001) are dominating in vitreal hyalocytes. While the comparison of the gene expression profiles of hyalocytes and other myeloid cell populations showed an overall strong similarity (R 2 > 0.637, p < 0.001), hyalocytes demonstrated significant differences with respect to common leukocyte-associated factors. In particular, transcripts involved in the immune privilege of the eye, such as POMC, CD46, and CD86, were significantly increased in hyalocytes compared to other myeloid cell subsets. Conclusion:Human hyalocytes represent a unique and distinct innate immune cell population specialized and adapted for the tissue-specific needs in the human vitreous. Vitreal hyalocytes are characterized by a strong expression of genes related to antigen processing and presentation as well as immune modulation. Thus, hyalocytes may represent an underestimated mediator in vitreoretinal disease and for the immune privilege of the eye.
| S-EPMC7517040 | biostudies-literature
Project description:<p>Healthy behavioral patterns could modulate organ functions to enhance the body’s immunity. However, whether exercise regulates antiviral innate immunity remains elusive. Here, we found that exercise promotes type-I IFN (IFN-I) production in the liver and enhances IFN-I immune activity of the body. Despite the possibility that many exercise-induced factors could regulate IFN-I production, we identified Gpld1 as a crucial molecule and the liver as the major organ to promote IFN-I production after exercise. Exercise largely loses the efficiency to induce IFN-I in Gpld1-/- mice. Further studies demonstrated that exercise-produced 3-hydroxybutanoic acid (3-HB) critically induces Gpld1 expression in the liver. Gpld1 blocks the PP2A-IRF3 interaction and therefore enhances IRF3 activation and IFN-I production, and improves the body’s antiviral ability. This study reveals that the exercise behavior improves antiviral innate immunity by linking the liver metabolism to systemic IFN-I activity, and uncovers an unknown function of liver cells in innate immunity.</p>
2024-04-24 | MTBLS7972 | MetaboLights
Project description:Transcriptional response by macrophages stimulated with selected cytokines or innate immune stimuli
2016-02-09 | E-MTAB-3255 | biostudies-arrayexpress
Project description:Transcriptional profiling of the innate immune response in bovine cells
| PRJNA767623 | ENA
Project description:Background and Aims: Recent identification of intracellular DNA sensing pathways and involvement in numerous diverse disease processes including viral pathogenesis and autoimmunity suggests a role for these processes in liver pathology. The presence of these pathways in the liver and their role in HBV infection is unknown. Methods: In order to characterize the role of DNA sensing pathways in the liver, we utilized in vitro models. Microarray was performed on DNA treated and HBV infected hepatoma primary human hepatocytes. Results: Here we show that HBV infection and foreign DNA results in a significant innate immune response characterized by the production of inflammatory chemokines. The goal of this study is to characterize the changes in gene expression triggered by HBV and foreign DNA in primary human hepatocytes. PHHs were infected with HBV (MO.I = 50) for 40 hours. PHHs were transfected with 1μg/mL of ISD/dsDNA90 for 12 or 24 hours. Three replicates were performed for each condition.
2016-08-09 | E-GEOD-69590 | biostudies-arrayexpress
Project description:This work uncovers a druggable chromatin crosstalk that defines tumor innate immune response and enables immune evasion.
2022-10-08 | GSE186239 | GEO
Project description:The innate immune system provides the first response to pathogen infection and orchestrates the activation of the adaptive immune system. Though a large component of the innate immune response is common to all infections, pathogen-specific innate immune responses have been documented as well. The innate immune response is thought to be especially critical for fighting infection with Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB). While TB can be a deadly disease, only 5-10% of individuals infected with MTB develop active disease, and this inter-individual variation is, at least partly, heritable. Studies of inter-individual variation in the innate immune response to MTB infection may therefore shed light on the genetic basis for variation in susceptibility to TB. Yet, to date, we still do not know which properties of the innate immune response are specific to MTB infection and which represent a general response to pathogen infection. To begin addressing this gap, we infected macrophages with eight different bacterial pathogens, including different MTB strains and related mycobacteria, and studied the transcriptional response to infection. We found that although the gene expression changes were largely consistent across the bacterial infection treatments, we were able to identify a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. Genetic variants that are associated with regulatory differences in these genes should be considered candidate loci for explaining inter-individual susceptibility TB. RNA-seq of monocyte-derived macrophages isolated from 6 healthy European males at 4, 18, and 48 hours post-infection with the following 8 bacteria: Mycobacterium tuberculosis (MTB) H37Rv, Mycobacterium tuberculosis GC1237, MTB GC1237, bacillus Calmette-Guérin (BCG), Mycobacterium smegmatis, Yersinia pseudotuberculosis, Salmonella typhimurium, and Staphylococcus epidermidis. table-s1.txt is a tab-delimited text file that contains the batch-corrected log2 counts per million for each of the 156 samples, as well as the Ensembl gene ID and gene name. BCG = bacillus Calmette-Guérin GC = Mycobacterium tuberculosis GC1237 Rv = Mycobacterium tuberculosis (MTB) H37Rv Rv+ = heat-inactivated MTB H37Rv Salm = Salmonella typhimurium Smeg = Mycobacterium smegmatis Staph = Staphylococcus epidermidis Yers = Yersinia pseudotuberculosis
2015-03-31 | E-GEOD-67427 | biostudies-arrayexpress
Project description:ALVAC-Comp was an NHP immunogenicity study designed to identify the temporal kinetics of innate immune activation by ALVAC-SIV vaccination. PAXGENE tubes were harvested at 16h, 24h, 48h and 72h post vaccination to investigate the speed, magnitude, and durability of ALVAC-SIV induced innate immune activation. This study was set up to identify the optimal timepoint(s) post-vaccination in which to probe the cellular and molecular signaling mechanisms of innate immunity induced by vaccination. Comparison of genes/pathways in common and unique to the 4 post-vaccination timepoints will reveal the order of innate immune induction post-vaccination.
2021-08-13 | GSE181996 | GEO
Project description:PAF1 knockout and ncgRNA control cells were treated with multiple innate immune stimuli for 3 hours to mimic various microbial stresses.
2022-04-10 | E-MTAB-11620 | biostudies-arrayexpress