scholarly journals Single-cell RNA-seq reveals endoimmune cells in zebrafish

2020 ◽  
Author(s):  
Yunwei Shi ◽  
Peipei Qian ◽  
Jiajing Sheng ◽  
Xu Zhang ◽  
Xiaoning Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Single Cell ◽  
Immune Cells ◽  
Innate Immune ◽  
Marker Genes ◽  
Innate Immune Cells ◽  
Sequencing Analysis ◽  
Rna Seq ◽  
And Function ◽  
Normal Physiological Function

AbstractEndothelial cells (ECs) constitute a monolayer that covers the interior surface of blood vessels and participates in various processes. Although vascular ECs share certain common properties, they differ in both structure and function. So far, the transcriptome profile and heterogeneity of the full repertoire of ECs in vertebrates remain poorly understood. The relatively small size of zebrafish embryos and larvae allows a feasible analysis of the broad spectrum of ECs within every tissue and organ of a whole organism. ECs have been suggested to be conditional innate immune cells. Whether ECs possess the comparable capacity of involvement in immune response is so far undetermined. Currently, through single-cell RNA sequencing analysis of total ECs of zebrafish we identified a fraction of endothelial cells expressing the marker genes of innate immune cells, named “endoimmune cells”. We found the percentage of these cells gradually increased along with the embryonic development. Then, we observed the patrolling mCherry+ cells displayed the morphology alike to the macrophages and neutrophils. Furthermore, we revealed that some of the kdrl:ras-mCherry ECs were labelled with coro1a:EGFP as well. In addition, we demonstrated that the mCherry+ EC from intersegmental vessel could gradually present the expression of GFP in Tg(kdrl:ras-mCherry∷coro1a:GFP) line, suggesting the endoimmune cells are derived from ECs. Importantly, we showed the endoimmune cells are responsive to the inflammation in zebrafish. Taken together, these data suggested the existence of endoimmune cells, a novel type of subpopulations of ECs. It will provide novel insights for understanding endothelial roles in both normal physiological function and human diseases and enable endoimmune cells-based target therapies.

scholarly journals An Interspecies Regulatory Network Inferred from Simultaneous RNA-seq of Candida albicans Invading Innate Immune Cells

2012 ◽  
Vol 3 ◽  
Author(s):  
Lanay Tierney ◽  
Jörg Linde ◽  
Sebastian Müller ◽  
Sascha Brunke ◽  
Juan Camilo Molina ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Immune Cells ◽  
Regulatory Network ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Rna Seq

scholarly journals An evolving new paradigm: endothelial cells – conditional innate immune cells

2013 ◽  
Vol 6 (1) ◽  
pp. 61 ◽  
Author(s):  
Jietang Mai ◽  
Anthony Virtue ◽  
Jerry Shen ◽  
Hong Wang ◽  
Xiao-Feng Yang
Keyword(s):  
Endothelial Cells ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
New Paradigm

scholarly journals A Novel Regulatory Player in the Innate Immune System: Long Non-Coding RNAs

2021 ◽  
Vol 22 (17) ◽  
pp. 9535
Author(s):  
Yuhuai Xie ◽  
Yuanyuan Wei
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Mediated ◽  
Development And Differentiation ◽  
Non Coding Rnas ◽  
And Function

Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.

scholarly journals Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular System

2021 ◽  
Vol 8 ◽  
Author(s):  
David R. Sweet ◽  
Cherry Lam ◽  
Mukesh K. Jain
Keyword(s):  
Endothelial Cells ◽  
Immune Cells ◽  
Inflammatory Diseases ◽  
Evolutionary Relationship ◽  
Nucleotide Composition ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Cellular Quiescence ◽  
Physiological Demands ◽  
Cellular Compartments

A properly functioning hemovascular system, consisting of circulating innate immune cells and endothelial cells (ECs), is essential in the distribution of nutrients to distant tissues while ensuring protection from invading pathogens. Professional phagocytes (e.g., macrophages) and ECs have co-evolved in vertebrates to adapt to increased physiological demands. Intercellular interactions between components of the hemovascular system facilitate numerous functions in physiology and disease in part through the utilization of shared signaling pathways and factors. Krüppel-like factors (KLFs) 2 and 4 are two such transcription factors with critical roles in both cellular compartments. Decreased expression of either factor in myeloid or endothelial cells increases susceptibility to a multitude of inflammatory diseases, underscoring the essential role for their expression in maintaining cellular quiescence. Given the close evolutionary relationship between macrophages and ECs, along with their shared utilization of KLF2 and 4, we hypothesize that KLF genes evolved in such a way that protected their expression in myeloid and endothelial cells. Within this Perspective, we review the roles of KLF2 and 4 in the hemovascular system and explore evolutionary trends in their nucleotide composition that suggest a coordinated protection that corresponds with the development of mature myeloid and endothelial systems.

scholarly journals Trained Immunity and Reactivity of Macrophages and Endothelial Cells

2020 ◽  
Author(s):  
Charles Drummer ◽  
Fatma Saaoud ◽  
Ying Shao ◽  
Yu Sun ◽  
Keman Xu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Tricarboxylic Acid Cycle ◽  
Density Lipoprotein ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Vaccine Response ◽  
Trained Immunity

Innate immune cells can develop exacerbated immunologic response and long-term inflammatory phenotype following brief exposure to endogenous or exogenous insults, which leads to an altered response towards a second challenge after the return to a nonactivated state. This phenomenon is known as trained immunity (TI). TI is not only important for host defense and vaccine response but also for chronic inflammations such as cardiovascular and metabolic diseases such as atherosclerosis. TI can occur in innate immune cells such as monocytes/macrophages, natural killer cells, endothelial cells (ECs), and nonimmune cells, such as fibroblast. In this brief review, we analyze the significance of TI in ECs, which are also considered as innate immune cells in addition to macrophages. TI can be induced by a variety of stimuli, including lipopolysaccharides, bacillus Calmette-Guerin, and oxLDL (oxidized low-density lipoprotein), which are defined as risk factors for cardiovascular and metabolic diseases. Furthermore, TI in ECs is functional for inflammation effectiveness and transition to chronic inflammation. Rewiring of cellular metabolism of the trained cells takes place during induction of TI, including increased glycolysis, glutaminolysis, increased accumulation of tricarboxylic acid cycle metabolites and acetyl-coenzyme A production, as well as increased mevalonate synthesis. Subsequently, this leads to epigenetic remodeling, resulting in important changes in chromatin architecture that enables increased gene transcription and enhanced proinflammatory immune response. However, TI pathways and inflammatory pathways are separated to ensure memory stays when inflammation undergoes resolution. Additionally, reactive oxygen species play context-dependent roles in TI. Therefore, TI plays significant roles in EC and macrophage pathology and chronic inflammation. However, further characterization of TI in ECs and macrophages would provide novel insights into cardiovascular disease pathogenesis and new therapeutic targets.

Phospholipase Cγ2 regulates endocannabinoid and eicosanoid networks in innate immune cells

2021 ◽  
Vol 118 (41) ◽  
pp. e2112971118
Author(s):  
Hui Jing ◽  
Alex Reed ◽  
Olesya A. Ulanovskaya ◽  
Jan-Sebastian Grigoleit ◽  
Dylan M. Herbst ◽  
...  
Keyword(s):  
Cross Talk ◽  
Immune Cells ◽  
Receptor Activation ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Genetic Studies ◽  
Mouse Macrophages ◽  
Inflammatory Stimuli ◽  
And Function ◽  
Human And Mouse

Human genetic studies have pointed to a prominent role for innate immunity and lipid pathways in immunological and neurodegenerative disorders. Our understanding of the composition and function of immunomodulatory lipid networks in innate immune cells, however, remains incomplete. Here, we show that phospholipase Cγ2 (PLCγ2 or PLCG2)—mutations in which are associated with autoinflammatory disorders and Alzheimer’s disease—serves as a principal source of diacylglycerol (DAG) pools that are converted into a cascade of bioactive endocannabinoid and eicosanoid lipids by DAG lipase (DAGL) and monoacylglycerol lipase (MGLL) enzymes in innate immune cells. We show that this lipid network is tonically stimulated by disease-relevant human mutations in PLCγ2, as well as Fc receptor activation in primary human and mouse macrophages. Genetic disruption of PLCγ2 in mouse microglia suppressed DAGL/MGLL-mediated endocannabinoid-eicosanoid cross-talk and also caused widespread transcriptional and proteomic changes, including the reorganization of immune-relevant lipid pathways reflected in reductions in DAGLB and elevations in PLA2G4A. Despite these changes, Plcg2−/− mice showed generally normal proinflammatory cytokine and chemokine responses to lipopolysaccharide treatment, instead displaying a more restricted deficit in microglial activation that included impairments in prostaglandin production and CD68 expression. Our findings enhance the understanding of PLCγ2 function in innate immune cells, delineating a role in cross-talk with endocannabinoid/eicosanoid pathways and modulation of subsets of cellular responses to inflammatory stimuli.

scholarly journals Development and function of human innate immune cells in a humanized mouse model

2014 ◽  
Vol 32 (4) ◽  
pp. 364-372 ◽  
Author(s):  
Anthony Rongvaux ◽  
Tim Willinger ◽  
Jan Martinek ◽  
Till Strowig ◽  
Sofia V Gearty ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
And Function
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