Role of Neuropeptides in the Regulation of the Insect Immune System – Current Knowledge and Perspectives

The immune system is receiving increasing attention for interstitial lung diseases, as knowledge on its role in fibrosis development and response to therapies is expanding. Uncontrolled immune responses and unbalanced injury-inflammation-repair processes drive the initiation and progression of idiopathic pulmonary fibrosis. The regulatory immune system plays important roles in controlling pathogenic immune responses, regulating inflammation and modulating the transition of inflammation to fibrosis. This review aims to summarize and critically discuss the current knowledge on the potential role of regulatory immune cells, including mesenchymal stromal/stem cells, regulatory T cells, regulatory B cells, macrophages, dendritic cells and myeloid-derived suppressor cells in idiopathic pulmonary fibrosis. Furthermore, we review the emerging role of regulatory immune cells in anti-fibrotic therapy and lung transplantation. A comprehensive understanding of immune regulation could pave the way towards new therapeutic or preventive approaches in idiopathic pulmonary fibrosis.

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Intracellular and Extracellular Roles of Granzyme K

Frontiers in Immunology ◽

10.3389/fimmu.2021.677707 ◽

2021 ◽

Vol 12 ◽

Author(s):

Annemieke C. Bouwman ◽

Kim R. van Daalen ◽

Sandra Crnko ◽

Toine ten Broeke ◽

Niels Bovenschen

Keyword(s):

Immune System ◽

Therapeutic Target ◽

Serine Proteases ◽

Bacterial Infections ◽

Thermal Injury ◽

Current Knowledge ◽

Endothelial Activation ◽

Potential Therapeutic Target ◽

Cytotoxic Cells

Granzymes are a family of serine proteases stored in granules inside cytotoxic cells of the immune system. Granzyme K (GrK) has been only limitedly characterized and knowledge on its molecular functions is emerging. Traditionally GrK is described as a granule-secreted, pro-apoptotic serine protease. However, accumulating evidence is redefining the functions of GrK by the discovery of novel intracellular (e.g. cytotoxicity, inhibition of viral replication) and extracellular roles (e.g. endothelial activation and modulation of a pro-inflammatory immune cytokine response). Moreover, elevated GrK levels are associated with disease, including viral and bacterial infections, airway inflammation and thermal injury. This review aims to summarize and discuss the current knowledge of i) intracellular and extracellular GrK activity, ii) cytotoxic and non-cytotoxic GrK functioning, iii) the role of GrK in disease, and iv) GrK as a potential therapeutic target.

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Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System

Frontiers in Immunology ◽

10.3389/fimmu.2021.767175 ◽

2021 ◽

Vol 12 ◽

Author(s):

Richard Felix Kraus ◽

Michael Andreas Gruber

Keyword(s):

Immune System ◽

Innate Immune System ◽

Current Knowledge ◽

Immune Defense ◽

Innate Immune ◽

Human Organism ◽

Polymorphonuclear Cells ◽

Target Tissue ◽

First Line

Neutrophils (polymorphonuclear cells; PMNs) form a first line of defense against pathogens and are therefore an important component of the innate immune response. As a result of poorly controlled activation, however, PMNs can also mediate tissue damage in numerous diseases, often by increasing tissue inflammation and injury. According to current knowledge, PMNs are not only part of the pathogenesis of infectious and autoimmune diseases but also of conditions with disturbed tissue homeostasis such as trauma and shock. Scientific advances in the past two decades have changed the role of neutrophils from that of solely immune defense cells to cells that are responsible for the general integrity of the body, even in the absence of pathogens. To better understand PMN function in the human organism, our review outlines the role of PMNs within the innate immune system. This review provides an overview of the migration of PMNs from the vascular compartment to the target tissue as well as their chemotactic processes and illuminates crucial neutrophil immune properties at the site of the lesion. The review is focused on the formation of chemotactic gradients in interaction with the extracellular matrix (ECM) and the influence of the ECM on PMN function. In addition, our review summarizes current knowledge about the phenomenon of bidirectional and reverse PMN migration, neutrophil microtubules, and the microtubule organizing center in PMN migration. As a conclusive feature, we review and discuss new findings about neutrophil behavior in cancer environment and tumor tissue.

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Microbiota and Hypertension: Role of the Sympathetic Nervous System and the Immune System

American Journal of Hypertension ◽

10.1093/ajh/hpaa103 ◽

2020 ◽

Cited By ~ 1

Author(s):

Iñaki Robles-Vera ◽

Marta Toral ◽

Juan Duarte

Keyword(s):

T Cells ◽

Nervous System ◽

Immune System ◽

Sympathetic Nervous System ◽

Gut Microbiota ◽

Current Knowledge ◽

Vascular Inflammation ◽

T Helper 17 ◽

Sympathetic Nervous

Abstract There are numerous studies indicating a direct association between hypertension and gut microbiota in both animal models and humans. In this review, we focused on the imbalance in the gut microbiota composition relative to healthy state or homeostasis, termed dysbiosis, associated with hypertension and discuss the current knowledge regarding how microbiota regulates blood pressure (BP), involving the sympathetic nervous system and the immune system. The profile of ecological parameters and bacterial genera composition of gut dysbiosis in hypertension varies according to the experimental model of hypertension. Recent evidence supports that gut microbiota can protect or promote the development of hypertension by interacting with gut secondary lymph organs and altering T helper 17/regulatory T cells polarization, with subsequent changes in T cells infiltration in vascular tissues. Here, we also describe the bidirectional communication between the microbiome and the host via the sympathetic nervous system and its role in BP regulation. Dysbiosis in hypertension is mainly associated with reduced proportions of short-chain fatty acid-producing bacteria, mainly acetate- and butyrate-producing bacteria, and an increased enrichment of the genes for lipopolysaccharide biosynthesis and export, lending to moderate endotoxemia. The role of these metabolic and structural products in both immune and sympathetic system regulation and vascular inflammation was also analyzed. Overall, gut microbiota is now recognized as a well-established target to dietary interventions with prebiotics or probiotics to reduce BP.

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Toward Understanding the Role of Aryl Hydrocarbon Receptor in the Immune System: Current Progress and Future Trends

BioMed Research International ◽

10.1155/2014/520763 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 38

Author(s):

Hamza Hanieh

Keyword(s):

Immune System ◽

Aryl Hydrocarbon Receptor ◽

Immune Cells ◽

Immune Cell ◽

Current Knowledge ◽

Physiological Role ◽

Clinical Practices ◽

Aryl Hydrocarbon ◽

Active Research

The immune system is regulated by distinct signaling pathways that control the development and function of the immune cells. Accumulating evidence suggest that ligation of aryl hydrocarbon receptor (Ahr), an environmentally responsive transcription factor, results in multiple cross talks that are capable of modulating these pathways and their downstream responsive genes. Most of the immune cells respond to such modulation, and many inflammatory response-related genes contain multiple xenobiotic-responsive elements (XREs) boxes upstream. Active research efforts have investigated the physiological role of Ahr in inflammation and autoimmunity using different animal models. Recently formed paradigm has shown that activation of Ahr by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3,3′-diindolylmethane (DIM) prompts the differentiation of CD4+Foxp3+regulatory T cells (Tregs) and inhibits T helper (Th)-17 suggesting that Ahr is an innovative therapeutic strategy for autoimmune inflammation. These promising findings generate a basis for future clinical practices in humans. This review addresses the current knowledge on the role of Ahr in different immune cell compartments, with a particular focus on inflammation and autoimmunity.

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Nutritional Modulation of Immune and Central Nervous System Homeostasis: The Role of Diet in Development of Neuroinflammation and Neurological Disease

Nutrients ◽

10.3390/nu11051076 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1076 ◽

Cited By ~ 8

Author(s):

José Antonio Estrada ◽

Irazú Contreras

Keyword(s):

Immune System ◽

Dietary Patterns ◽

Neurological Disease ◽

Metabolic Diseases ◽

Current Knowledge ◽

Treg Cells ◽

Signaling Molecules ◽

Metabolic Alterations ◽

Microbiome Composition

The gut-microbiome-brain axis is now recognized as an essential part in the regulation of systemic metabolism and homeostasis. Accumulating evidence has demonstrated that dietary patterns can influence the development of metabolic alterations and inflammation through the effects of nutrients on a multitude of variables, including microbiome composition, release of microbial products, gastrointestinal signaling molecules, and neurotransmitters. These signaling molecules are, in turn, implicated in the regulation of the immune system, either promoting or inhibiting the production of pro-inflammatory cytokines and the expansion of specific leukocyte subpopulations, such as Th17 and Treg cells, which are relevant in the development of neuroinflammatory and neurodegenerative conditions. Metabolic diseases, like obesity and type 2 diabetes mellitus, are related to inadequate dietary patterns and promote variations in the aforementioned signaling pathways in patients with these conditions, which have been linked to alterations in neurological functions and mental health. Thus, maintenance of adequate dietary patterns should be an essential component of any strategy aiming to prevent neurological pathologies derived from systemic metabolic alterations. The present review summarizes current knowledge on the role of nutrition in the modulation of the immune system and its impact in the development of neuroinflammation and neurological disease.

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The role of the immune system in idiopathic nephrotic syndrome

Molecular and Cellular Pediatrics ◽

10.1186/s40348-021-00128-6 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Agnes Hackl ◽

Seif El Din Abo Zed ◽

Paul Diefenhardt ◽

Julia Binz-Lotter ◽

Rasmus Ehren ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Immune System ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Idiopathic Nephrotic Syndrome ◽

Cell Subset ◽

Causative Factor ◽

Direct Role ◽

Filtration Barrier

AbstractIdiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia and usually responds well to steroids. However, relapses are frequent, which can require multi-drug therapy with deleterious long-term side effects. In the last decades, different hypotheses on molecular mechanisms underlying INS have been proposed and several lines of evidences strongly indicate a crucial role of the immune system in the pathogenesis of non-genetic INS. INS is traditionally considered a T-cell-mediated disorder triggered by a circulating factor, which causes the impairment of the glomerular filtration barrier and subsequent proteinuria. Additionally, the imbalance between Th17/Tregs as well as Th2/Th1 has been implicated in the pathomechanism of INS. Interestingly, B-cells have gained attention, since rituximab, an anti-CD20 antibody demonstrated a good therapeutic response in the treatment of INS. Finally, recent findings indicate that even podocytes can act as antigen-presenting cells under inflammatory stimuli and play a direct role in activating cellular pathways that cause proteinuria. Even though our knowledge on the underlying mechanisms of INS is still incomplete, it became clear that instead of a traditionally implicated cell subset or one particular molecule as a causative factor for INS, a multi-step control system including soluble factors, immune cells, and podocytes is necessary to prevent the occurrence of INS. This present review aims to provide an overview of the current knowledge on this topic, since advances in our understanding of the immunopathogenesis of INS may help drive new tailored therapeutic approaches forward.

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Endoglin: An ‘Accessory’ Receptor Regulating Blood Cell Development and Inflammation

International Journal of Molecular Sciences ◽

10.3390/ijms21239247 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9247

Author(s):

Steffen K. Meurer ◽

Ralf Weiskirchen

Keyword(s):

Endothelial Cells ◽

Immune System ◽

Immune Cells ◽

Transforming Growth Factor ◽

Current Knowledge ◽

Vascular Lesions ◽

Type I ◽

And Function ◽

Tgf Β1

Transforming growth factor-β1 (TGF-β1) is a pleiotropic factor sensed by most cells. It regulates a broad spectrum of cellular responses including hematopoiesis. In order to process TGF-β1-responses in time and space in an appropriate manner, there is a tight regulation of its signaling at diverse steps. The downstream signaling is mediated by type I and type II receptors and modulated by the ‘accessory’ receptor Endoglin also termed cluster of differentiation 105 (CD105). Endoglin was initially identified on pre-B leukemia cells but has received most attention due to its high expression on activated endothelial cells. In turn, Endoglin has been figured out as the causative factor for diseases associated with vascular dysfunction like hereditary hemorrhagic telangiectasia-1 (HHT-1), pre-eclampsia, and intrauterine growth restriction (IUPR). Because HHT patients often show signs of inflammation at vascular lesions, and loss of Endoglin in the myeloid lineage leads to spontaneous inflammation, it is speculated that Endoglin impacts inflammatory processes. In line, Endoglin is expressed on progenitor/precursor cells during hematopoiesis as well as on mature, differentiated cells of the innate and adaptive immune system. However, so far only pro-monocytes and macrophages have been in the focus of research, although Endoglin has been identified in many other immune system cell subsets. These findings imply a functional role of Endoglin in the maturation and function of immune cells. Aside the functional relevance of Endoglin in endothelial cells, CD105 is differentially expressed during hematopoiesis, arguing for a role of this receptor in the development of individual cell lineages. In addition, Endoglin expression is present on mature immune cells of the innate (i.e., macrophages and mast cells) and the adaptive (i.e., T-cells) immune system, further suggesting Endoglin as a factor that shapes immune responses. In this review, we summarize current knowledge on Endoglin expression and function in hematopoietic precursors and mature hematopoietic cells of different lineages.

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An overview of the human immune system and the role of interferon regulatory factors (IRFs)

Progress In Microbes & Molecular Biology ◽

10.36877/pmmb.a0000129 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Ashwinder Kaur ◽

Chee-Mun Fang

Keyword(s):

Immune System ◽

Regulatory Networks ◽

Current Knowledge ◽

Dynamic Network ◽

Defense Responses ◽

Human Immune System ◽

Regulatory Factors ◽

Interferon Regulatory Factors ◽

Essential Components

The immune system consists of a dynamic network of cells, proteins, tissues, and organs that communicate to provide adequate defense responses against pathogenic agents. The immune system divide into the non-specific (innate) and the specific (adaptive) components, where the interactions between these two arms are intricately regulated. To deploy effective immune responses, immune systems comprise various cells and molecules that communicate with each other via signaling pathways coordinated by gene regulatory networks. The interferon regulatory factors (IRFs) are critical regulators of both the immune system’s development and activation of different cells. To better understand the essential components of the normal immune system, this review essentially aims to cover the current knowledge of individual components of the immune system and the important role of IRFs in regulating the immune system.

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Cells of the Immune System in Cardiac Remodeling: Main Players in Resolution of Inflammation and Repair After Myocardial Infarction

Frontiers in Immunology ◽

10.3389/fimmu.2021.664457 ◽

2021 ◽

Vol 12 ◽

Author(s):

Irina Kologrivova ◽

Marina Shtatolkina ◽

Tatiana Suslova ◽

Vyacheslav Ryabov

Keyword(s):

Myocardial Infarction ◽

Immune System ◽

Immune Cells ◽

Ventricular Remodeling ◽

Current Knowledge ◽

Left Ventricular Remodeling ◽

Left Ventricular ◽

Resolution Of Inflammation ◽

Anti Inflammatory

The burden of heart failure (HF), developing after myocardial infarction MI, still represents a major issue in clinical practice. Failure of appropriate resolution of inflammation during post-myocardial injury is associated with unsuccessful left ventricular remodeling and underlies HF pathogenesis. Cells of the immune system have been shown to mediate both protective and damaging effects in heart remodeling. This ambiguity of the role of the immune system and inconsistent results of the recent clinical trials question the benefits of anti-inflammatory therapies during acute MI. The present review will summarize knowledge of the roles that different cells of the immune system play in the process of post-infarct cardiac healing. Data on the phenotype, active molecules and functions of the immune cells, based on the results of both experimental and clinical studies, will be provided. For some cellular subsets, such as macrophages, neutrophils, dendritic cells and lymphocytes, an anti-inflammatory activity has been attributed to the specific subpopulations. Activity of other cells, such as eosinophils, mast cells, natural killer (NK) cells and NKT cells has been shown to be highly dependent of the signals created by micro-environment. Also, new approaches for classification of cellular phenotypes based on the single-cell RNA sequencing allow better understanding of the phenotype of the cells involved in resolution of inflammation. Possible perspectives of immune-mediated therapy for AMI patients are discussed in the conclusion. We also outline unresolved questions that need to be solved in order to implement the current knowledge on the role of the immune cells in post-MI tissue repair into practice.

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