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 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 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 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 Extracellular vesicle– and particle-mediated communication shapes innate and adaptive immune responses

2021 ◽  
Vol 218 (8) ◽  
Author(s):  
Fanny A. Pelissier Vatter ◽  
Michele Cioffi ◽  
Samer J. Hanna ◽  
Ines Castarede ◽  
Simone Caielli ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Extracellular Vesicle ◽  
Mediated Communication ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Regulatory Effects

Intercellular communication among immune cells is vital for the coordination of proper immune responses. Extracellular vesicles and particles (EVPs) act as messengers in intercellular communication, with important consequences for target cell and organ physiology in both health and disease. Under normal physiological conditions, immune cell–derived EVPs participate in immune responses by regulating innate and adaptive immune responses. EVPs play a major role in antigen presentation and immune activation. On the other hand, immune cell–derived EVPs exert immunosuppressive and regulatory effects. Consequently, EVPs may contribute to pathological conditions, such as autoimmune and inflammatory diseases, graft rejection, and cancer progression and metastasis. Here, we provide an overview of the role of EVPs in immune homeostasis and pathophysiology, with a particular focus on their contribution to innate and adaptive immunity and their potential use for immunotherapies.

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 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.

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

scholarly journals NF-κB in Cancer Immunity: Friend or Foe?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 355
Author(s):  
Guilhem Lalle ◽  
Julie Twardowski ◽  
Yenkel Grinberg-Bleyer
Keyword(s):  
Immune Responses ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Transcriptional Activators ◽  
New Class ◽  
Complex Interactions ◽  
Cancer Immunity ◽  
Distinct Cell ◽  
Cancer Initiation ◽  
Cancer Outcome

The emergence of immunotherapies has definitely proven the tight relationship between malignant and immune cells, its impact on cancer outcome and its therapeutic potential. In this context, it is undoubtedly critical to decipher the transcriptional regulation of these complex interactions. Following early observations demonstrating the roles of NF-κB in cancer initiation and progression, a series of studies converge to establish NF-κB as a master regulator of immune responses to cancer. Importantly, NF-κB is a family of transcriptional activators and repressors that can act at different stages of cancer immunity. In this review, we provide an overview of the selective cell-intrinsic contributions of NF-κB to the distinct cell types that compose the tumor immune environment. We also propose a new view of NF-κB targeting drugs as a new class of immunotherapies for cancer.

Sign in / Sign up

Export Citation Format

Share Document