scholarly journals CytokineLink: a cytokine communication map to analyse immune responses in inflammatory and infectious diseases

2021 ◽  
Author(s):  
Marton L Olbei ◽  
John Thomas ◽  
Isabelle Hautefort ◽  
Agatha Treveil ◽  
Balazs Bohar ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Intercellular Communication ◽  
Interaction Network ◽  
Cell Types ◽  
Target Cells ◽  
Small Molecular Weight ◽  
Systems Immunology ◽  
Cytokine Interactions

Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine - cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from literature, and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated literature information on cell - cytokine interactions from two systems immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell-cell communication network connected by cytokines; and a cytokine-cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify inactive cell types and cytokine interactions that may be important following SARS-CoV-2 infection when comparing the cytokine response with other viruses capable of initiating a cytokine storm. Such findings have potential to inform the development of novel, cytokine-targeted therapeutic strategies. CytokineLink is freely available for the scientific community through the NDEx platform and the project github repository (https://github.com/korcsmarosgroup/CytokineLink).

scholarly journals CytokineLink: A Cytokine Communication Map to Analyse Immune Responses—Case Studies in Inflammatory Bowel Disease and COVID-19

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2242
Author(s):  
Marton Olbei ◽  
John P. Thomas ◽  
Isabelle Hautefort ◽  
Agatha Treveil ◽  
Balazs Bohar ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immune Responses ◽  
Intercellular Communication ◽  
Inflammatory Diseases ◽  
Interaction Network ◽  
Cell Types ◽  
Severe Illness ◽  
Target Cells ◽  
Small Molecular Weight ◽  
Cytokine Interactions

Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine–cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from the literature and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated the literature information on cell–cytokine interactions from two systems of immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell–cell communication network connected by cytokines; and a cytokine–cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink, we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify cell types and cytokine interactions following SARS-CoV-2 infection, highlighting important cytokine interactions that might contribute to severe illness in a subgroup of patients. Such findings have the potential to inform the development of novel, cytokine-targeted therapeutic strategies. CytokineLink is freely available for the scientific community through the NDEx platform and the project github repository.

scholarly journals P020 Mapping the changing intercellular communication and its downstream effect in Ulcerative Colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S138-S139
Author(s):  
L Potari-gul ◽  
D Modos ◽  
D Turei ◽  
A Valdeolivas ◽  
M Madgwick ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Single Cell ◽  
Intercellular Communication ◽  
Cell Types ◽  
Cell Junctions ◽  
Target Cells ◽  
Downstream Effects ◽  
Cell Cell

Abstract Background Intercellular communication is essential for growing and differentiating in multicellular organisms by transducing the signal from cell to cell. Despite its importance, the molecular background is less discovered due to the lack of data. This gap has started to be addressed with the appearance of single-cell omics approaches providing an insight among others into the gene expression of individual cells. Methods We have developed a method to predict and compare cell-cell signalling interactions using single-cell RNAseq data from colon biopsies. Transcriptomic data alone is not capable of connecting the cells, a reliable network resource is needed to mediate the signal via protein-protein interactions between the source and target cells. Here we used OmniPath - a resource providing not only intra- and intercellular interactions but also annotations of proteins involved in the interplay of cells - to reconstruct signalling networks. We examined intercellular communication among five cell-types (regulatory T cell, macrophage, dendritic cell, goblet cell and myofibroblast) in healthy colon and during Ulcerative Colitis. Results Our analysis shows that there are significant differences in the type of cell-cell communication (ligand-receptor connections, adherens junctions, etc.) between the healthy and Ulcerative Colitis (UC) conditions, and these differences lead to altered downstream effects in the signal receiving cell. In both conditions, the ligand-receptor and adhesion connections were overrepresented, however cell junctions were less abundant in UC. Regarding the communication among the five cell-types, in healthy condition, cells are tightly connected to dendritic cells while in diseased condition to regulatory T cells. Focusing on ligand-receptor interactions between myofibroblasts and regulatory T cells, our pipeline identified the MAPK, Toll-like receptor (TLR) 2/6 and TLR 7/8 pathways enriched downstream in healthy conditions. In contrast, TLR3 and TLR4 pathways were affected by the myofibroblast in Ulcerative Colitis. Conclusion We found key intercellular mechanisms leading to well-defined differential pathway activation profiles. We showed that in uninflamed UC condition myofibroblasts disrupt the anti-inflammatory effect of regulatory T cells. Our pipeline is able to predict and analyse cell-cell interactions and their downstream effects and to highlight the differences in healthy and diseased states.

scholarly journals Lipid Nanoparticles as Delivery Systems for RNA-Based Vaccines

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 206 ◽  
Author(s):  
Basmah N. Aldosari ◽  
Iman M. Alfagih ◽  
Alanood S. Almurshedi
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Viral Vectors ◽  
Cost Effective ◽  
Lipid Nanoparticles ◽  
Target Cells ◽  
Efficient Delivery ◽  
Preclinical And Clinical Studies ◽  
Cancer Immunotherapies ◽  
Conventional Vaccine

There has been increased interest in the development of RNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies. Rapid and cost-effective manufacturing methods in addition to potent immune responses observed in preclinical and clinical studies have made mRNA-based vaccines promising alternatives to conventional vaccine technologies. However, efficient delivery of these vaccines requires that the mRNA be protected against extracellular degradation. Lipid nanoparticles (LNPs) have been extensively studied as non-viral vectors for the delivery of mRNA to target cells because of their relatively easy and scalable manufacturing processes. This review highlights key advances in the development of LNPs and reviews the application of mRNA-based vaccines formulated in LNPs for use against infectious diseases and cancer.

scholarly journals Exosome-Based Vaccines: History, Current State, and Clinical Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Patrick Santos ◽  
Fausto Almeida
Keyword(s):  
Clinical Trials ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Cell Types ◽  
Biological Functions ◽  
Current State ◽  
Wide Range ◽  
Different Types ◽  
Dendritic Cell Vaccines ◽  
Delivery Mechanism

Extracellular vesicles (EVs) are released by most cell types as part of an intracellular communication system in crucial processes such as inflammation, cell proliferation, and immune response. However, EVs have also been implicated in the pathogenesis of several diseases, such as cancer and numerous infectious diseases. An important feature of EVs is their ability to deliver a wide range of molecules to nearby targets or over long distances, which allows the mediation of different biological functions. This delivery mechanism can be utilized for the development of therapeutic strategies, such as vaccination. Here, we have highlighted several studies from a historical perspective, with respect to current investigations on EV-based vaccines. For example, vaccines based on exosomes derived from dendritic cells proved to be simpler in terms of management and cost-effectiveness than dendritic cell vaccines. Recent evidence suggests that EVs derived from cancer cells can be leveraged for therapeutics to induce strong anti-tumor immune responses. Moreover, EV-based vaccines have shown exciting and promising results against different types of infectious diseases. We have also summarized the results obtained from completed clinical trials conducted on the usage of exosome-based vaccines in the treatment of cancer, and more recently, coronavirus disease.

scholarly journals Vitamin D and the Immune System

2021 ◽  
Author(s):  
Vikram Singh Chauhan
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Immune Responses ◽  
Interleukin 1 ◽  
Cell Types ◽  
Surface Proteins ◽  
Target Cells ◽  
B Cell Differentiation ◽  
Regulatory T Lymphocytes ◽  
Factor Α

In the past few decades, various novel actions of vitamin D have been discovered. The mechanism of action of calcitriol or vitamin D is mediated by the Vitamin D receptor (VDR), a subfamily of nuclear receptors, which acts as a transcription factor in the target cells after formation of a heterodimer with the retinoid X receptor (RXR). As the VDR has been found in virtually all cell types, vitamin D exerts multiple actions on different tissues. Vitamin D has important immunomodulatory actions, which includes enhancement of the innate immune system and inhibition of the adaptative immune responses. These actions are associated with an increase in production of interleukin (IL)-4 by T helper (Th)-2 lymphocytes and the up-regulation of regulatory T lymphocytes. Vitamin D can regulate the immune responses in secondary lymphoid organs as well as in target organs through a number of mechanisms. Vitamin D inhibits the expression of APC cytokines, such as interleukin-1 (IL-1), IL-6, IL-12, and tissue necrosis factor- α (TNF-α) and decreases the expression of a set of major histocompatibility complex (MCH) class II cell surface proteins in macrophages. Vitamin D also inhibits B cell differentiation and antibody production. These actions reflect an important role of Vitamin D in balancing the immune system.

scholarly journals Imaging flow cytometry challenges the usefulness of classically used EV labelling dyes and qualifies that of a novel dye, named Exoria for the labelling of MSC-EV preparations

2021 ◽  
Author(s):  
Tobias Tertel ◽  
Melanie Schoppet ◽  
Oumaima Stambouli ◽  
Ali Al-Jipouri ◽  
Patrick F. James ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Intercellular Communication ◽  
Fluorescent Dyes ◽  
Immune Cell ◽  
Cell Types ◽  
Target Cells ◽  
Phenotypic Analysis ◽  
Imaging Flow Cytometry ◽  
Communication Processes ◽  
Calcein Am

Extracellular vesicles (EVs) are involved in mediating intercellular communication processes. An important goal within the EV field is the study of the biodistribution of EVs and the identification of their target cells. Considering that EV uptake is central for mediating the EVs role in intercellular communication processes, labelling with fluorescent dyes has emerged as a broadly distributed strategy for the identification of the EVs target cells and tissues. However, the accuracy and specificity of commonly utilized labelling dyes has not been sufficiently analyzed. By combining recent advancements in imaging flow cytometry for the phenotypic analysis of single EVs and aiming to identify target cells for EVs within therapeutically relevant MSC-EV preparations, we explored the EV labelling efficacy of various fluorescent dyes, specifically of CFDA-SE, Calcein AM, PKH67, BODIPY-TR-Ceramide and a novel lipid dye named Exoria. Our analyses qualified Exoria as the only dye which specifically labels EVs within our MSC-EV preparations. Furthermore, we demonstrate Exoria labelling does not interfere with the immunomodulatory properties of the MSC-EV preparations as tested in a multi-donor mixed lymphocyte reaction assay. Within this assay, labelled EVs were differentially taken-up by different immune cell types. Overall, our results qualify Exoria as an appropriate dye for the labelling of EVs derived from our MSC-EV preparations, this study also demonstrates the need for the development of next generation EV characterization tools which are able to localize and confirm specificity of EV labelling.

scholarly journals Cancer systems immunology

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nathan E Reticker-Flynn ◽  
Edgar G Engleman
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Tumor Immunology ◽  
Cell Types ◽  
Emergent Behavior ◽  
Multiple Time ◽  
Omics Technologies ◽  
Systems Immunology ◽  
Organ Systems ◽  
Size Scales

Tumor immunology is undergoing a renaissance due to the recent profound clinical successes of tumor immunotherapy. These advances have coincided with an exponential growth in the development of –omics technologies. Armed with these technologies and their associated computational and modeling toolsets, systems biologists have turned their attention to tumor immunology in an effort to understand the precise nature and consequences of interactions between tumors and the immune system. Such interactions are inherently multivariate, spanning multiple time and size scales, cell types, and organ systems, rendering systems biology approaches particularly amenable to their interrogation. While in its infancy, the field of ‘Cancer Systems Immunology’ has already influenced our understanding of tumor immunology and immunotherapy. As the field matures, studies will move beyond descriptive characterizations toward functional investigations of the emergent behavior that govern tumor-immune responses. Thus, Cancer Systems Immunology holds incredible promise to advance our ability to fight this disease.

scholarly journals Extracellular Vesicles from Healthy Cells Improves Cell Function and Stemness in Premature Senescent Stem Cells by miR-302b and HIF-1α Activation

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 957
Author(s):  
Cristina Mas-Bargues ◽  
Jorge Sanz-Ros ◽  
Aurora Román-Domínguez ◽  
Lucia Gimeno-Mallench ◽  
Marta Inglés ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Cell Function ◽  
Cell Types ◽  
Culture Conditions ◽  
Target Cells ◽  
Activity Levels ◽  
Functional Changes

Aging is accompanied by the accumulation of senescent cells that alter intercellular communication, thereby impairing tissue homeostasis and reducing organ regenerative potential. Recently, the administration of mesenchymal stem cells (MSC)-derived extracellular vesicles has proven to be more effective and less challenging than current stem cell-based therapies. Extracellular vesicles (EVs) contain a cell-specific cargo of proteins, lipids and nucleic acids that are released and taken up by probably all cell types, thereby inducing functional changes via the horizontal transfer of their cargo. Here, we describe the beneficial properties of extracellular vesicles derived from non-senescent MSC, cultured in a low physiological oxygen tension (3%) microenvironment into prematurely senescent MSC, cultured in a hyperoxic ambient (usual oxygen culture conditions, i.e., 21%). We observed that senescent MCS, treated with EVs from non-senescent MCS, showed reduced SA-β-galactosidase activity levels and pluripotency factor (OCT4, SOX2, KLF4 and cMYC, or OSKM) overexpression and increased glycolysis, as well as reduced oxidative phosphorylation (OXPHOS). Moreover, these EVs’ cargo induced the upregulation of miR-302b and HIF-1α levels in the target cells. We propose that miR-302b triggered HIF-1α upregulation, which in turn activated different pathways to delay premature senescence, improve stemness and switch energetic metabolism towards glycolysis. Taken together, we suggest that EVs could be a powerful tool to restore altered intercellular communication and improve stem cell function and stemness, thus delaying stem cell exhaustion in aging.

scholarly journals Fostering “Education”: Do Extracellular Vesicles Exploit Their Own Delivery Code?

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1741
Author(s):  
Mayra Paolillo ◽  
Sergio Comincini ◽  
Sergio Schinelli
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Surface Membrane ◽  
Cell Types ◽  
Future Research ◽  
Target Cells ◽  
Bioinformatic Tools ◽  
Experimental Approaches ◽  
Different Cell Types

Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV “delivery code” and on the combinations of the hypothesized EV surface membrane “sender” and “recipient” molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.

Two way relationship of pregnancy and immune responses to infectious diseases

Placenta ◽  
1996 ◽  
Vol 17 (5-6) ◽  
pp. A10
Author(s):  
L. Krishnan ◽  
L.J. Guilbert ◽  
T.G. Wegmann ◽  
M. Belosevic ◽  
T.R. Mosmann
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Relationship Of
Sign in / Sign up

Export Citation Format

Share Document