scholarly journals The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Xing ◽  
Xun Sun ◽  
Yiming Dou ◽  
Min Wang ◽  
Yanmei Zhao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Extracellular Vesicles ◽  
Inflammatory Diseases ◽  
Gastrointestinal Disease ◽  
Biological Functions ◽  
Modulation Effect ◽  
Chronic Inflammatory Diseases ◽  
Pathological Conditions ◽  
Potential Applications ◽  
Regulatory Effects

As natural nanocarriers and intercellular messengers, extracellular vesicles (EVs) control communication among cells. Under physiological and pathological conditions, EVs deliver generic information including proteins and nucleic acids to recipient cells and exert regulatory effects. Macrophages help mediate immune responses, and macrophage-derived EVs may play immunomodulatory roles in the progression of chronic inflammatory diseases. Furthermore, EVs derived from various macrophage phenotypes have different biological functions. In this review, we describe the pathophysiological significance of macrophage-derived extracellular vesicles in the development of chronic inflammatory diseases, including diabetes, cancer, cardiovascular disease, pulmonary disease, and gastrointestinal disease, and the potential applications of these EVs.

scholarly journals Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 167 ◽  
Author(s):  
Muhammad Nawaz ◽  
Neelam Shah ◽  
Bruna Zanetti ◽  
Marco Maugeri ◽  
Renata Silvestre ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Metabolic Diseases ◽  
Bioactive Molecules ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Pathological Conditions ◽  
Potential Applications ◽  
Non Coding Rnas

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

scholarly journals Modulation of Autophagy for Controlling Immunity

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 138 ◽  
Author(s):  
Young Jin Jang ◽  
Jae Hwan Kim ◽  
Sanguine Byun
Keyword(s):  
Immune Responses ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Mechanisms Of Action ◽  
Innate And Adaptive Immunity ◽  
Pathological Conditions ◽  
Physiological Homeostasis ◽  
Autophagy Pathway ◽  
Key Steps ◽  
Additional Role

Autophagy is an essential process that maintains physiological homeostasis by promoting the transfer of cytoplasmic constituents to autophagolysosomes for degradation. In immune cells, the autophagy pathway plays an additional role in facilitating proper immunological functions. Specifically, the autophagy pathway can participate in controlling key steps in innate and adaptive immunity. Accordingly, alterations in autophagy have been linked to inflammatory diseases and defective immune responses against pathogens. In this review, we discuss the various roles of autophagy signaling in coordinating immune responses and how these activities are connected to pathological conditions. We highlight the therapeutic potential of autophagy modulators that can impact immune responses and the mechanisms of action responsible.

scholarly journals Targeting Opposing Immunological Roles of the Junctional Adhesion Molecule-A in Autoimmunity and Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Caio S. Bonilha ◽  
Robert A. Benson ◽  
James M. Brewer ◽  
Paul Garside
Keyword(s):  
Immune Responses ◽  
Adhesion Molecule ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Clinical Pathology ◽  
Surface Adhesion ◽  
Pathological Conditions ◽  
Relevant Role ◽  
A Cell ◽  
Cell Surface Adhesion Molecule

The junctional adhesion molecule-A (JAM-A) is a cell surface adhesion molecule expressed on platelets, epithelial cells, endothelial cells and leukocytes (e. g. monocytes and dendritic cells). JAM-A plays a relevant role in leukocyte trafficking and its therapeutic potential has been studied in several pathological conditions due to its capacity to induce leukocyte migration out of inflamed sites or infiltration into tumor sites. However, disruption of JAM-A pathways may worsen clinical pathology in some cases. As such, the effects of JAM-A manipulation on modulating immune responses in the context of different diseases must be better understood. In this mini-review, we discuss the potential of JAM-A as a therapeutic target, summarizing findings from studies manipulating JAM-A in the context of inflammatory diseases (e.g. autoimmune diseases) and cancer and highlighting described mechanisms.

scholarly journals Cross talk between neutrophils and the microbiota

Blood ◽  
2019 ◽  
Vol 133 (20) ◽  
pp. 2168-2177 ◽  
Author(s):  
Dachuan Zhang ◽  
Paul S. Frenette
Keyword(s):  
Immune Responses ◽  
Cross Talk ◽  
Inflammatory Diseases ◽  
Host Immunity ◽  
Host Immune System ◽  
Chronic Inflammatory Diseases ◽  
Important Regulator ◽  
Cellular Mediators ◽  
Functional Modulation ◽  
And Function

Abstract The microbiota has emerged as an important regulator of the host immunity by the induction, functional modulation, or suppression of local and systemic immune responses. In return, the host immune system restricts translocation and fine tunes the composition and distribution of the microbiota to maintain a beneficial symbiosis. This paradigm applies to neutrophils, a critical component of the innate immunity, allowing their production and function to be influenced by microbial components and metabolites derived from the microbiota, and engaging them in the process of microbiota containment and regulation. The cross talk between neutrophils and the microbiota adjusts the magnitude of neutrophil-mediated inflammation on challenge while preventing neutrophil responses against commensals under steady state. Here, we review the major molecular and cellular mediators of the interactions between neutrophils and the microbiota and discuss their interplay and contribution in chronic inflammatory diseases and cancer.

scholarly journals Exaggerated in vivo IL-17 responses discriminate recall responses in active TB

2019 ◽  
Author(s):  
Gabriele Pollara ◽  
Carolin T Turner ◽  
Gillian S Tomlinson ◽  
Lucy CK Bell ◽  
Ayesha Khan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Th17 Cells ◽  
Latent Infection ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases ◽  
Host Immune Responses ◽  
Matrix Metalloproteinase 1 ◽  
First Time

AbstractHost immune responses at the site of Mycobacterium tuberculosis (Mtb) infection serve to contain the pathogen, but also mediate the pathogenesis of tuberculosis (TB) and onward transmission of infection. Interferon gamma (IFNγ) responses do not discriminate between protection and pathogenicity, but IL-17A/F responses, known to drive pathology in diverse chronic inflammatory diseases, have also been associated with TB pathogenesis in animal models. At the site of in vivo immune recall responses to Mtb modelled by the tuberculin skin test, we show for the first time that active TB in humans is also associated with exaggerated IL-17A/F expression, accumulation of Th17 cells and IL-17A/F bioactivity, including increased neutrophil recruitment and matrix metalloproteinase-1 expression directly implicated in TB pathogenesis. These features discriminate recall responses in patients with active TB from those with cured or latent infection and are also evident at the site of TB disease. Our data support targeting of this pathway in host-directed therapy for TB.

scholarly journals Schistosome-Derived Molecules as Modulating Actors of the Immune System and Promising Candidates to Treat Autoimmune and Inflammatory Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Luis Janssen ◽  
Gisele Lorranna Silva Santos ◽  
Herick Sampaio Muller ◽  
Anderson Rodrigues Araújo Vieira ◽  
Tatiana Amabile de Campos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Defense Mechanisms ◽  
Inflammatory Diseases ◽  
Adaptive Responses ◽  
Immunomodulatory Effects ◽  
Larval Stages ◽  
Helminth Infections ◽  
Autoimmune And Inflammatory Diseases ◽  
Potential Applications ◽  
Parasite Infections

It is long known that some parasite infections are able to modulate specific pathways of host’s metabolism and immune responses. This modulation is not only important in order to understand the host-pathogen interactions and to develop treatments against the parasites themselves but also important in the development of treatments against autoimmune and inflammatory diseases. Throughout the life cycle of schistosomes the mammalian hosts are exposed to several biomolecules that are excreted/secreted from the parasite infective stage, named cercariae, from their tegument, present in adult and larval stages, and finally from their eggs. These molecules can induce the activation and modulation of innate and adaptive responses as well as enabling the evasion of the parasite from host defense mechanisms. Immunomodulatory effects of helminth infections and egg molecules are clear, as well as their ability to downregulate proinflammatory cytokines, upregulate anti-inflammatory cytokines, and drive a Th2 type of immune response. We believe that schistosomes can be used as a model to understand the potential applications of helminths and helminth-derived molecules against autoimmune and inflammatory diseases.

scholarly journals Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1βProduction

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
József Tőzsér ◽  
Szilvia Benkő
Keyword(s):  
Immune Responses ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Mechanistic Explanation ◽  
Natural Compounds ◽  
The Other ◽  
Oxygen Species ◽  
Molecular Tools ◽  
Chronic Inflammatory Diseases ◽  
Physiological Processes

IL-1βis one of the main proinflammatory cytokines that regulates a broad range of immune responses and also participates in several physiological processes. The canonical production of IL-1βrequires multiprotein complexes called inflammasomes. One of the most intensively studied inflammasome complexes is the NLRP3 inflammasome. Its activation requires two signals: one signal “primes” the cells and induces the expression of NLRP3 and pro-IL-1β, while the other signal leads to the assembly and activation of the complex. Several stimuli were reported to function as the second signal including reactive oxygen species, lysosomal rupture, or cytosolic ion perturbation. Despite very intensive studies, the precise function and regulation of the NLRP3 inflammasome are still not clear. However, many chronic inflammatory diseases are related to the overproduction of IL-1βthat is mediatedviathe NLRP3 inflammasome. In this review, we aimed to provide an overview of studies that demonstrated the effect of plant-derived natural compounds on NLRP3 inflammasome-mediated IL-1βproduction. Although many of these studies lack the mechanistic explanation of their action, these compounds may be considered as complementary supplements in the treatment of chronic inflammatory diseases, consumed as preventive agents, and may also be considered as molecular tools to study NLRP3 function.

scholarly journals Joint Reconstituted Signaling of the IL-6 Receptor via Extracellular Vesicles

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1307 ◽  
Author(s):  
Philipp Arnold ◽  
Wiebke Lückstädt ◽  
Wenjia Li ◽  
Inga Boll ◽  
Juliane Lokau ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Biological Functions ◽  
Pathological Conditions ◽  
Stat3 Phosphorylation ◽  
Attractive Therapeutic Target ◽  
Anti Inflammatory ◽  
Β Receptor ◽  
Almost All ◽  
Transcription 3 ◽  
Regulatory Event

Interleukin-6 (IL-6) signaling is a crucial regulatory event important for many biological functions, such as inflammation and tissue regeneration. Accordingly, several pathological conditions are associated with dysregulated IL-6 activity, making it an attractive therapeutic target. For instance, blockade of IL-6 or its α-receptor (IL-6R) by monoclonal antibodies has been successfully used to treat rheumatoid arthritis. However, based on different signaling modes, IL-6 function varies between pro- and anti-inflammatory activity, which is critical for therapeutic intervention. So far, three modes of IL-6 signaling have been described, the classic anti-inflammatory signaling, as well as pro-inflammatory trans-signaling, and trans-presentation. The IL-6/IL-6R complex requires an additional β-receptor (gp130), which is expressed on almost all cells of the human body, to induce STAT3 (signal transducer and activator of signal transcription 3) phosphorylation and subsequent transcriptional regulation. In contrast, the IL-6R is expressed on a limited number of cells, including hepatocytes and immune cells. However, the proteolytic release of the IL-6R enables trans-signaling on cells expressing gp130 only. Here, we demonstrate a fourth possibility of IL-6 signaling that we termed joint reconstituted signaling (JRS). We show that IL-6R on extracellular vesicles (EVs) can also be transported to and fused with other cells that lack the IL-6R on their surface. Importantly, JRS via EVs induces delayed STAT3 phosphorylation compared to the well-established trans-signaling mode. EVs isolated from human serum were already shown to carry the IL-6R, and thus this new signaling mode should be considered with regard to signal intervention.

scholarly journals Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

2018 ◽  
Vol 2018 ◽  
pp. 1-25 ◽  
Author(s):  
Luca Parisi ◽  
Elisabetta Gini ◽  
Denisa Baci ◽  
Marco Tremolati ◽  
Matteo Fanuli ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Cancer Type ◽  
Effector Cells ◽  
Chronic Inflammatory Diseases ◽  
Pathological Conditions ◽  
Cellular Components ◽  
Cell Cell

Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

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