Repeated stimulation of self-presentation pathway by targeting erythrocytes in vivo drives anergy and profound T cell dysfunction
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE155679 | GEO | 2021/02/26
REPOSITORIES: GEO
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Project description:Repeated stimulation of self-presentation pathway by targeting erythrocytes in vivo drives anergy and profound T cell dysfunction
| PRJNA655210 | ENA
Project description:We employed high-throughput sequencing of both short (~18-24nt) and long (>200nt) RNAs in human erythrocytes. We obtained blood from five healthy individuals for the short (small) RNA-seq library preparations and blood from three individuals for the long RNA-seq library preparations. We identified an abundant, diverse population of RNAs. Both polyadenylated and nonpolyadenlated long RNAs were identified. Additionally, known and novel microRNAs were identified in the short RNA dataset using the probabalistic modeling algorithm miRDeep. These RNAs lend insight into erythrocyte biology and provide utility as potential biomarkers. To determine both shared and unique aspects of the erythrocyte long RNA transcriptome, we compared this transcriptome with that of the PBMC and CD34+ erythroid progenitor transcriptomes. Sequencing of RNAs from mature erythrocytes of healthy individuals
2015-11-19 | E-GEOD-63703 | biostudies-arrayexpress
Project description:Purpose: This study identifies the top transcripts expressed in mature erythrocytes and the top transcripts expressed in the polysome fractions of mature erythrocyte lysate Methods: RNA from total erythrocyte lysate and polysome fractions was isolated and purified using GeneJet RNA purification column (Thermo Fisher Scientific). The RNA library was prepared using NEBNext ULTRA II RNA library preparation kit for Illumina. The libraries were sequenced using Illumina Seq. Results: The transcriptome analysis revealed the abundance of mRNAs encoding globins genes, long non-coding RNAs, and micro RNAs. Deciphering the role and functions of these non-coding RNAs in these specialised cells could enable us to understand their biology in greater detail
2019-03-22 | GSE128648 | GEO
Project description:Neutrophils and erythrocytes are vital to the immune system and oxygen transport, respectively. However, the mechanisms by which hematopoietic niches support their development remain incompletely understood. In hematopoiesis research, zebrafish larvae are a common model for studying the development of definitive neutrophils and erythrocytes in the caudal hematopoietic tissue. In this study, we showed that erythrocytes predominantly reside inside the blood vessels of the CHT, while neutrophils stay outside. Ectopic vascular endothelium, induced by Bone Morphogenetic Protein 2b(Bmp2b) overexpression, attracts both cell types, with erythrocytes inside and neutrophils outside. CHT removal has minimal impact on definitive neutrophils from the ventral wall of the dorsal aorta (VDA) but severely affects definitive erythrocytes from the same source. Bulk RNA-sequencing identified epoa as a vital factor for erythrocyte generation within CHT endothelium. Overexpression of epoa through the lyve1b promoter, which is specifically expressed in vein, lymphatic vessels and CHT vein endothelial cells, rescued the erythrocyte reduction in epoa mutants. Our study reveals that the caudal hematopoietic tissue is differentially required for definitive erythrocytes and neutrophils.
2023-11-16 | GSE247730 | GEO
Project description:We employed high-throughput sequencing of both short (~18-24nt) and long (>200nt) RNAs in human erythrocytes. We obtained blood from five healthy individuals for the short (small) RNA-seq library preparations and blood from three individuals for the long RNA-seq library preparations. We identified an abundant, diverse population of RNAs. Both polyadenylated and nonpolyadenlated long RNAs were identified. Additionally, known and novel microRNAs were identified in the short RNA dataset using the probabalistic modeling algorithm miRDeep. These RNAs lend insight into erythrocyte biology and provide utility as potential biomarkers. To determine both shared and unique aspects of the erythrocyte long RNA transcriptome, we compared this transcriptome with that of the PBMC and CD34+ erythroid progenitor transcriptomes.
2015-11-19 | GSE63703 | GEO
Project description:Understanding gene expression changes over the lifespan of cells is of fundamental interest and gives important insights into processes related to maturation and ageing. This study was undertaken to understand the global transcriptome changes associated with ageing in fish erythrocytes. Fish erythrocytes retain their nuclei throughout their lifetime and they are transcriptionally and translationally active. However, they lose important functions during their lifespan in the circulation. We separated rainbow trout (Oncorhynchus mykiss) erythrocytes into young and old fractions using fixed angle-centrifugation and analyzed transcriptome changes using RNA sequencing (RNA-seq) technology and quantitative real-time PCR. We found 930 differentially expressed between young and old erythrocyte fractions; 889 of these showed higher transcript levels in young, while only 34 protein-coding genes had higher transcript levels in old erythrocytes. In particular ion binding, signal transduction, membrane transport, and various enzyme classes are affected in old erythrocytes. The transcripts with higher levels in old erythrocytes were associated with 7 different GO terms within biological processes and 9 within molecular functions and cellular components respectively. Our study furthermore found several highly abundant transcripts as well as a number of differentially expressed genes for which the protein products are currently not known revealing the gaps of knowledge in most non-mammalian vertebrates. Our data provide the first insight into changes involved in ageing on the transcriptional level and thus opens new perspectives for the study of maturation processes in fish erythrocytes.
2018-02-13 | GSE106570 | GEO
Project description:Erythrocytes are the most numerous cells of the human body (Sender 2016). Their lifespan in the blood stream is around 120 days. The turnover implies the production of 2 million new reticulocytes each second. Circulating reticulocytes achieve their maturation in 2 to 3 days. During this short time, important modifications occur such as membrane remodeling, removing of remaining organelles and specific elimination of useless proteins such as the transferrin receptor. This remodeling will ensure the optimization of the erythrocyte ability to fulfil its transport functions. We performed a deep label-free quantitative proteome analysis of purified erythrocytes and reticulocytes to better understand the physiology of the erythrocytes and the last steps of their maturation.
2018-09-18 | PXD009258 | Pride
Project description:Plasmodium falciparum causes the most severe form of malaria in humans. The protozoan parasite develops within erythrocytes to mature schizonts, that contain more than 16 merozoites, which egress and invade fresh erythrocytes. The aspartic protease plasmepsin X (PMX), processes proteins and proteases essential for merozoite egress from the schizont and invasion of the host erythrocyte, including the leading vaccine candidate PfRh5. PfRh5 is anchored to the merozoite surface through a 5-membered complex (PCRCR), consisting of Plasmodium thrombospondin-related apical merozoite protein (PTRAMP), cysteine-rich small secreted protein (CSS), Rh5-interacting protein (PfRipr) and cysteine-rich protective antigen (CyRPA). We show that PCRCR is processed by PMX in micronemes to remove the N-terminal prodomain and this activates the function of the complex unmasking a form that can bind basigin on the erythrocyte membrane and mediate merozoite invasion. The ability to activate PCRCR at a specific time in merozoite invasion ensures invasion inhibitory epitopes are exposed to the immune system for a minimal time but also mask potential deleterious effects of its function until they are required. These results provide an important understanding of the essential roles of PMX and the fine regulation of PCRCR function in P. falciparum biology.
2023-04-05 | PXD039646 | Pride
Project description:Our group has recently shown induction of antigen-specific T cell tolerance through targeting antigen to erythrocytes in situ, based on the premise that as the erythrocytes age and are cleared eryptotically, their carried antigen payload is processed tolerogenically. The tolerogenic state is characterized by initial proliferation of antigen-specific CD4+ and CD8+ T cells, and subsequent acquisition of deletional, anergic and CD25+FOXP3+ regulatory T cell phenotypes. In this study, we wished to further understand the molecular mechanisms behind induction of tolerance by erythrocyte-targeted antigens. RNA sequencing was performed to determine how genes are regulated in tolerized ovalbumin-specific CD8+ T cells and which pathways are activated after treatment with this technology. High similarity between the gene response reported during self-tolerance, deletional tolerance and tolerance induced by erythrocyte-targeted antigens was observed. Treatment with erythrocyte-targeted antigens led to the upregulation of genes encoding several TCR co-inhibitory receptors such as CTLA4, PD1, LAG3, TIGIT and CD200R1, and lack of upregulation of cytotoxic and pro-inflammatory signaling molecule genes. Modulation in expression of the master transcription factors Egr2/NFatc1, Nur77 family and E2f1 was also observed, all known to be associated with the process of peripheral tolerance. Expression of these genes differed in response to treatment with soluble ovalbumin or free SIINFEKL MHCI peptide, suggesting a specific mechanism of T cell modulation and tolerance induction in response to the erythrocyte-associated forms. Together these results provide novel insights to further understand the mechanisms and potential of erythrocyte-targeted antigens for induction of antigen-specific immune tolerance.
2020-05-05 | GSE98590 | GEO
Project description:Transcriptome of mature erythrocytes
| PRJNA528391 | ENA