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The Journal of Allergy and Clinical... Feb 2018The goal of this series is to offer a survey of the latest literature for clinicians and scientists alike, providing a list of important recent advances relevant to the...
The goal of this series is to offer a survey of the latest literature for clinicians and scientists alike, providing a list of important recent advances relevant to the broad field of allergy and immunology. This particular assignment was to cover the topic of eosinophils. In an attempt to highlight major ideas, themes, trends, and advances relevant to basic and clinical aspects of eosinophil biology, a search of articles published since 2015 in the Journal of Allergy and Clinical Immunology and other high-impact journals was performed. Articles were then reviewed and organized, and then key findings were summarized. Given space limitations, many outstanding articles could not be included, but the hope is that what follows provides a succinct overview of recently published work that has significantly added to our knowledge of eosinophils and eosinophil-associated diseases.
Topics: Eosinophils; Humans; Immune System Diseases
PubMed: 29045815
DOI: 10.1016/j.jaci.2017.09.022 -
Biochemical Pharmacology Sep 2020Eosinophils are a type of granulated innate immune cells that have long been implicated in a specific type of asthma, referred to as eosinophilic asthma. Several... (Review)
Review
Eosinophils are a type of granulated innate immune cells that have long been implicated in a specific type of asthma, referred to as eosinophilic asthma. Several immunotherapeutics that target and deplete eosinophils or limit their numbers are currently widely used and provide improved disease outcome in severe eosinophilic asthma. Current clinical results provide conclusive evidence of a generally detrimental role of eosinophils in asthma. Yet, a small but growing body of reports suggests that eosinophils may be more diverse than currently appreciated. In this review, we explore pre-clinical and clinical evidence that suggests the existence of eosinophil subsets with potentially distinct functional roles in asthma. We conclude by discussing state-of-the-art strategies for deciphering heterogeneity of this complex cell type, and argue this knowledge could translate into the improved personalized treatment of severe eosinophilic asthma.
Topics: Animals; Asthma; Disease Models, Animal; Eosinophils; Humans; Lung
PubMed: 32278006
DOI: 10.1016/j.bcp.2020.113963 -
Allergie Et Immunologie Dec 1991There is controversy on functions, ranging from protective, tissue protecting to aggressive tissue damaging effects. High numbers are found in many diseases. The cell is... (Review)
Review
There is controversy on functions, ranging from protective, tissue protecting to aggressive tissue damaging effects. High numbers are found in many diseases. The cell is invariably seen when helminths invade tissues, with numbers correlated with IgE titres and it is the major cytotoxic cell for parasitic larvae. It is produced by bone marrow, and controlled by T cell products and other mediators. A fundamental connection exists between asthma and eosinophils irrespective of the presence of an allergic factor. Study of sputum samples is of more value than blood eosinophil numbers. After allergen challenge there may be both immediate and late reactions. Where the late reaction occurs blood eosinophil numbers rise, indicating a central position in the pathogenesis. Cellular proteins and extracellular products and their effects are tabulated. The cells are heterogenous into two types, normodense (low activity) and hypodense which have high activity of increased secretory activity, chemotactic response etc. Treatments for asthma and beta-2-agonists and corticosteroids inhibit mediator release and eosinophil numbers and the abnormality should be considered early.
Topics: Asthma; Cytokines; Cytoplasmic Granules; Eosinophilia; Eosinophils; Humans; Immunoglobulin E; Lymphokines; T-Lymphocytes
PubMed: 1811647
DOI: No ID Found -
International Journal of Molecular... Jun 2021Eosinophils are specialized white blood cells, which are involved in the pathology of diverse allergic and nonallergic inflammatory diseases. Eosinophils are... (Review)
Review
Eosinophils are specialized white blood cells, which are involved in the pathology of diverse allergic and nonallergic inflammatory diseases. Eosinophils are traditionally known as cytotoxic effector cells but have been suggested to additionally play a role in immunomodulation and maintenance of homeostasis. The exact role of these granule-containing leukocytes in health and diseases is still a matter of debate. Degranulation is one of the key effector functions of eosinophils in response to diverse stimuli. The different degranulation patterns occurring in eosinophils (piecemeal degranulation, exocytosis and cytolysis) have been extensively studied in the last few years. However, the exact mechanism of the diverse degranulation types remains unknown and is still under investigation. In this review, we focus on recent findings and highlight the diversity of stimulation and methods used to evaluate eosinophil degranulation.
Topics: Cell Degranulation; Eosinophils; Extracellular Traps; Humans; Hypersensitivity
PubMed: 34209362
DOI: 10.3390/ijms22137091 -
Seminars in Immunopathology Jun 2021Eosinophils are granule-containing leukocytes which develop in the bone marrow. For many years, eosinophils have been recognized as cytotoxic effector cells, but recent... (Review)
Review
Eosinophils are granule-containing leukocytes which develop in the bone marrow. For many years, eosinophils have been recognized as cytotoxic effector cells, but recent studies suggest that they perform additional immunomodulatory and homeostatic functions. Autophagy is a conserved intracellular process which preserves cellular homeostasis. Autophagy defects have been linked to the pathogenesis of many human disorders. Evidence for abnormal regulation of autophagy, including decreased or increased expression of autophagy-related (ATG) proteins, has been reported in several eosinophilic inflammatory disorders, such as Crohn's disease, bronchial asthma, eosinophilic esophagitis, and chronic rhinosinusitis. Despite the increasing extent of research using preclinical models of immune cell-specific autophagy deficiency, the physiological relevance of autophagic pathway in eosinophils has remained unknown until recently. Owing to the increasing evidence that eosinophils play a role in keeping organismal homeostasis, the regulation of eosinophil functions is of considerable interest. Here, we discuss the most recent advances on the role of autophagy in eosinophils, placing particular emphasis on insights obtained in mouse models of infections and malignant diseases in which autophagy has genetically dismantled in the eosinophil lineage. These studies pointed to the possibility that autophagy-deficient eosinophils exaggerate inflammation. Therefore, the pharmacological modulation of the autophagic pathway in these cells could be used for therapeutic interventions.
Topics: Asthma; Autophagy; Eosinophils; Homeostasis; Humans; Inflammation
PubMed: 34019141
DOI: 10.1007/s00281-021-00860-1 -
Clinical Reviews in Allergy & Immunology Apr 2016First described by Paul Ehrlich in 1879, who noted its characteristic staining by acidophilic dyes, for many years, the eosinophil was considered to be an end-effector... (Review)
Review
First described by Paul Ehrlich in 1879, who noted its characteristic staining by acidophilic dyes, for many years, the eosinophil was considered to be an end-effector cell associated with helminth infections and a cause of tissue damage. Over the past 30 years, research has helped to elucidate the complexity of the eosinophil's function and establish its role in host defense and immunity. Eosinophils express an array of ligand receptors which play a role in cell growth, adhesion, chemotaxis, degranulation, and cell-to-cell interactions. They play a role in activation of complement via both classical and alternative pathways. Eosinophils synthesize, store and secrete cytokines, chemokines, and growth factors. They can process antigen, stimulate T cells, and promote humoral responses by interacting with B cells. Eosinophils can function as antigen presenting cells and can regulate processes associated with both T1 and T2 immunity. Although long known to play a role in defense against helminth organisms, the interactions of eosinophils with these parasites are now recognized to be much more complex. In addition, their interaction with other pathogens continues to be investigated. In this paper, we review the eosinophil's unique biology and structure, including its characteristic granules and the effects of its proteins, our developing understanding of its role in innate and adaptive immunity and importance in immunomodulation, and the part it plays in defense against parasitic, viral, fungal and bacterial infections. Rather than our worst enemy, the eosinophil may, in fact, be one of the most essential components in host defense and immunity.
Topics: Adaptive Immunity; Animals; Cell Differentiation; Chemotaxis; Cytokines; Eosinophils; Humans; Immunity, Innate; Infections; Inflammation Mediators; Membrane Proteins
PubMed: 26690368
DOI: 10.1007/s12016-015-8525-4 -
Cells Feb 2021Eosinophilic asthma is the most prevalent phenotype of asthma. Although most asthmatics are adequately controlled by corticosteroid therapy, a subset (5-10%) remain... (Review)
Review
Eosinophilic asthma is the most prevalent phenotype of asthma. Although most asthmatics are adequately controlled by corticosteroid therapy, a subset (5-10%) remain uncontrolled with significant therapy-related side effects. This indicates the need for a consideration of alternative treatment strategies that target airway eosinophilia with corticosteroid-sparing benefits. A growing body of evidence shows that a balance between systemic differentiation and local tissue eosinophilopoietic processes driven by traffic and lung homing of bone marrow-derived hemopoietic progenitor cells (HPCs) are important components for the development of airway eosinophilia in asthma. Interleukin (IL)-5 is considered a critical and selective driver of terminal differentiation of eosinophils. Studies targeting IL-5 or IL-5R show that although mature and immature eosinophils are decreased within the airways, there is incomplete ablation, particularly within the bronchial tissue. Eotaxin is a chemoattractant for mature eosinophils and eosinophil-lineage committed progenitor cells (EoP), yet anti-CCR3 studies did not yield meaningful clinical outcomes. Recent studies highlight the role of epithelial cell-derived alarmin cytokines, IL-33 and TSLP, (Thymic stromal lymphopoietin) in progenitor cell traffic and local differentiative processes. This review provides an overview of the role of EoP in asthma and discusses findings from clinical trials with various therapeutic targets. We will show that targeting single mediators downstream of the inflammatory cascade may not fully attenuate tissue eosinophilia due to the multiplicity of factors that can promote tissue eosinophilia. Blocking lung homing and local eosinophilopoiesis through mediators upstream of this cascade may yield greater improvement in clinical outcomes.
Topics: Animals; Asthma; Cell Lineage; Eosinophils; Hematopoiesis; Humans; Molecular Targeted Therapy; Stem Cells
PubMed: 33669458
DOI: 10.3390/cells10020412 -
Memorias Do Instituto Oswaldo Cruz 1997While the eosinophil's effector functions clearly can contribute to the pathogenesis of allergic diseases, the evolutionary benefit to having eosinophils as a distinct... (Review)
Review
While the eosinophil's effector functions clearly can contribute to the pathogenesis of allergic diseases, the evolutionary benefit to having eosinophils as a distinct class of leukocyte is not clear, especially if one must reconsider the nominally beneficial role of eosinophils in parasite host defense, Eosinophils are equipped to respond to lymphocytes and their cytokines (and not solely the eosinophil growth factor cytokines), but the functional consequences of such eosinophil responses need to be defined. Conversely, eosinophils, as antigen-presenting cells (APCs) or sources of lymphocyte-active cytokines, may stimulate and affect lymphocyte functioning. Eosinophils share with CD4+ lymphocytes expression of a number of receptors, including CD4 and IL-2R, and specific alpha-4 integrins that may help in their common recruitment and activation. Further, elucidation of the interactions between lymphocytes and eosinophils will contribute to a broader understanding of the functioning of eosinophils in "normal" ongoing immune responses and in allergic disorders.
Topics: Cell Communication; Cytokines; Eosinophils; Humans; Hypersensitivity; Lymphocytes
PubMed: 9698930
DOI: 10.1590/s0074-02761997000800023 -
The Journal of Allergy and Clinical... Jan 2020Eosinophilic esophagitis (EoE) is an eosinophil-rich, T2 antigen-mediated disease of increasing pediatric and adult worldwide prevalence. Diagnosis requires greater than... (Review)
Review
Eosinophilic esophagitis (EoE) is an eosinophil-rich, T2 antigen-mediated disease of increasing pediatric and adult worldwide prevalence. Diagnosis requires greater than or equal to 15 eosinophils per high-power field on light microscopy. Symptoms reflect esophageal dysfunction, and typical endoscopic features include linear furrows, white plaques, and concentric rings. Progressive disease leads to pathologic tissue remodeling, with ensuing esophageal rigidity and loss of luminal diameter caused by strictures. Therapies include proton pump inhibitors, elimination diets, and topical corticosteroids. Effective treatment can reverse tissue fibrosis in some patients, as well as decrease the rate of food impactions. Esophageal dilation might be required to increase luminal patency. The chronic nature of EoE necessitates long-term therapy to avoid disease recurrence and complications. This review serves the function of providing the current state-of-the-art diagnostic criteria and disease management for adult and pediatric EoE.
Topics: Adrenal Cortex Hormones; Diet Therapy; Eosinophilic Esophagitis; Eosinophils; Esophagus; Humans; Proton Pump Inhibitors
PubMed: 31910983
DOI: 10.1016/j.jaci.2019.11.011 -
Basic & Clinical Pharmacology &... Jan 2014Asthma is a chronic inflammatory disease of the airways manifesting in many different phenotypes. Allergic asthma, comprising approximately half of patients with asthma,... (Review)
Review
Asthma is a chronic inflammatory disease of the airways manifesting in many different phenotypes. Allergic asthma, comprising approximately half of patients with asthma, is characterized by the accumulation of eosinophils into the lungs. Eosinophils release factors that damage the surrounding cells and participate in the maintenance and exacerbation of inflammation. In the absence of any inflammatory survival-prolonging factors, eosinophils die by apoptosis in few days but in inflamed airways, eosinophil survival is thought to be prolonged due to the surrounding pro-inflammatory factors such as IL-5, IL-3 and GM-CSF. Resolution of eosinophilic inflammation is an important goal in the treatment of allergic asthma. Apoptosis is a physiological and non-inflammatory way to eliminate these harmful cells, and development of drugs targeting eosinophil apoptosis is one possible strategy for the therapy of allergic asthma. Importance of this strategy is supported by the fact that promotion of eosinophil apoptosis is a property of many anti-asthmatic agents such as glucocorticoids, the current main anti-inflammatory therapy of asthma, theophylline and leukotriene modifiers. β2 agonists have been shown to modulate eosinophil longevity by increasing survival. Also, anti-IL-5 antibody mesolizumab has shown efficacy in reducing asthma exacerbations in patients with severe eosinophilic asthma. Many potential future anti-asthmatic agents, such as Siglec-8 activating antibody and novel humanized anti-IL-5 antibody MEDI-563, have the property of inducing eosinophil apoptosis. This MiniReview aims to present eosinophil apoptosis as a therapeutic target in the treatment of allergic asthma. We summarize the effects and mechanisms of current and potential future anti-asthmatic drugs on eosinophil apoptosis and additionally, discuss the potential factors that promote eosinophil longevity in the lungs.
Topics: Animals; Anti-Asthmatic Agents; Apoptosis; Asthma; Disease Models, Animal; Eosinophils; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation; Interleukin-3; Interleukin-5; Lung
PubMed: 24148899
DOI: 10.1111/bcpt.12163