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International Journal of Molecular... Feb 2019Interleukin (IL)-18 was originally discovered as a factor that enhanced IFN-γ production from anti-CD3-stimulated Th1 cells, especially in the presence of IL-12. Upon... (Review)
Review
Interleukin (IL)-18 was originally discovered as a factor that enhanced IFN-γ production from anti-CD3-stimulated Th1 cells, especially in the presence of IL-12. Upon stimulation with Ag plus IL-12, naïve T cells develop into IL-18 receptor (IL-18R) expressing Th1 cells, which increase IFN-γ production in response to IL-18 stimulation. Therefore, IL-12 is a commitment factor that induces the development of Th1 cells. In contrast, IL-18 is a proinflammatory cytokine that facilitates type 1 responses. However, IL-18 without IL-12 but with IL-2, stimulates NK cells, CD4⁺ NKT cells, and established Th1 cells, to produce IL-3, IL-9, and IL-13. Furthermore, together with IL-3, IL-18 stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine. Therefore, IL-18 is a cytokine that stimulates various cell types and has pleiotropic functions. IL-18 is a member of the IL-1 family of cytokines. IL-18 demonstrates a unique function by binding to a specific receptor expressed on various types of cells. In this review article, we will focus on the unique features of IL-18 in health and disease in experimental animals and humans.
Topics: Animals; Disease Susceptibility; Gene Expression Regulation; Humans; Immune System; Interleukin-18; Interleukin-33; Molecular Targeted Therapy; Protein Binding; Receptors, Interleukin-18; Signal Transduction
PubMed: 30717382
DOI: 10.3390/ijms20030649 -
Annual Review of Pathology Jan 2017Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost... (Review)
Review
Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost productivity, and lost time at work and leading to more than a million surgical interventions annually worldwide. The nose, paranasal sinuses, and associated lymphoid tissues play important roles in homeostasis and immunity, and CRS significantly impairs these normal functions. Pathogenic mechanisms of CRS have recently become the focus of intense investigations worldwide, and significant progress has been made. The two main forms of CRS that have been long recognized, with and without nasal polyps, are each now known to be heterogeneous, based on underlying mechanism, geographical location, and race. Loss of the immune barrier, including increased permeability of mucosal epithelium and reduced production of important antimicrobial substances and responses, is a common feature of many forms of CRS. One form of CRS with polyps found worldwide is driven by the cytokines IL-5 and IL-13 coming from Th2 cells, type 2 innate lymphoid cells, and probably mast cells. Type 2 cytokines activate inflammatory cells that are implicated in the pathogenic mechanism, including mast cells, basophils, and eosinophils. New classes of biological drugs that block the production or action of these cytokines are making important inroads toward new treatment paradigms in polypoid CRS.
Topics: Adult; Chronic Disease; Humans; Nasal Polyps; Rhinitis; Sinusitis
PubMed: 27959637
DOI: 10.1146/annurev-pathol-052016-100401 -
Cytokine Sep 2015Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections... (Review)
Review
Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these "type 2 immune response-related" cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses. In this review, I will focus on the signaling pathways and key molecules that determine the differentiation of naïve CD4 T cells into Th2 cells, and how the expression of Th2 cytokines, especially IL-4 and IL-13, is regulated in Th2 cells. The similarities and differences in the differentiation of Th2 cells, IL-4-producing T follicular helper (Tfh) cells and ILC2s as well as their relationships will also be discussed.
Topics: Animals; Asthma; Cell Differentiation; Chromatin; Eosinophils; GATA3 Transcription Factor; Humans; Hypersensitivity; Immunity, Innate; Inflammation; Interleukin-13; Interleukin-4; Lymphocyte Activation; Lymphocytes; Mast Cells; Receptors, Antigen, T-Cell; Receptors, Notch; STAT5 Transcription Factor; Signal Transduction; Th2 Cells
PubMed: 26044597
DOI: 10.1016/j.cyto.2015.05.010 -
Trends in Parasitology Oct 2018Helminth infections represent a significant public health concern resulting in devastating morbidity and economic consequences across the globe. Helminths migrate... (Review)
Review
Helminth infections represent a significant public health concern resulting in devastating morbidity and economic consequences across the globe. Helminths migrate through mucosal sites causing tissue damage and the induction of type 2 immune responses. Antihelminth protection relies on the mobilization and activation of multiple immune cells, including type 2 innate lymphocytes (ILC2s), basophils, mast cells, macrophages, and hematopoietic stem/progenitor cells. Further, epithelial cells and neurons have been recognized as important regulators of type 2 immunity. Collectively, these pathways stimulate host-protective responses necessary for worm expulsion and the healing of affected tissues. In this review we focus on the innate immune pathways that regulate immunity to helminth parasites and describe how better understanding of these pathways may lead to the development of new therapeutic strategies.
Topics: Animals; Helminthiasis; Helminths; Host-Parasite Interactions; Humans; Immunity, Innate
PubMed: 30177466
DOI: 10.1016/j.pt.2018.08.007 -
Journal of Investigational Allergology... Dec 2022The life-threatening nature of anaphylactic reactions has increased interest in discovering new biomarkers that could improve diagnosis and prevention. However, the... (Review)
Review
The life-threatening nature of anaphylactic reactions has increased interest in discovering new biomarkers that could improve diagnosis and prevention. However, the diverse nature of the clinical features and the etiology and pathogenesis of anaphylaxis hinder the identification of valuable molecular indicators of disease. Most studies on anaphylaxis focus on the immune system. Anaphylactic reactions are characterized primarily by IgE-mediated activation of mast cells and basophils and release of mediators. Determination of serum tryptase levels is the main in vitro test used to confirm the reaction, although there are no biomarkers that can predict it. Nevertheless, recent research has postulated that alternative pathways, cell types, and systems are involved. Consequently, various molecular products have been explored and considered potential biomarkers, although none of them are yet used in clinical practice. The products that are altered in patients with anaphylaxis include vasoactive agents, proteases, proteoglycans, lipids, interleukins, cytokines, products of the complement-contact and coagulation systems, circulating proteins, extracellular vesicles, microRNAs, and metabolites. The recognition of biological processes and molecular pathways affecting the microenvironments involved in anaphylaxis will considerably improve clinical practice and the identification of better molecular markers. We offer a broad review of the various mediators described in anaphylaxis, consider their usefulness as potential biomarkers of this pathological event, and examine their role in the molecular basis of the reaction.
Topics: Humans; Anaphylaxis; Basophils; Mast Cells; Biomarkers; Cytokines
PubMed: 36000824
DOI: 10.18176/jiaci.0854 -
Allergy Jul 2021IgE, the key molecule in atopy has been shown to bind two receptors, FcεRI, the high-affinity receptor, and FcεRII (CD23), binding IgE with lower affinity. Whereas... (Review)
Review
IgE, the key molecule in atopy has been shown to bind two receptors, FcεRI, the high-affinity receptor, and FcεRII (CD23), binding IgE with lower affinity. Whereas cross-linking of IgE on FcεRI expressed by mast cells and basophils triggers the allergic reaction, binding of IgE to CD23 on B cells plays an important role in both IgE regulation and presentation. Furthermore, IgE-immune complexes (IgE-ICs) bound by B cells enhance antibody and T cell responses in mice and humans. However, the mechanisms that regulate the targeting of the two receptors and the respective function of the two pathways in inflammation or homeostasis are still a matter of debate. Here, we focus on CD23 and discuss several mechanisms related to IgE binding, as well as the impact of the IgE/antigen-binding on different immune cells expressing CD23. One recent paper has shown that free IgE preferentially binds to FcεRI whereas IgE-ICs are preferentially captured by CD23. Binding of IgE-ICs to CD23 on B cells can, on one hand, regulate serum IgE and prevent effector cell activation and on the other hand facilitate antigen presentation by delivering the antigen to dendritic cells. These data argue for a multifunctional role of CD23 for modulating IgE serum levels and immune responses.
Topics: Animals; Antigen Presentation; Antigens; B-Lymphocytes; Humans; Hypersensitivity; Immunoglobulin E; Mice; Receptors, IgE
PubMed: 33378583
DOI: 10.1111/all.14724 -
F1000Research 2017Chronic urticaria is a spontaneous or inducible group of diseases characterized by the occurrence of wheals (and, in about half of cases, angioedema) for more than 6... (Review)
Review
Chronic urticaria is a spontaneous or inducible group of diseases characterized by the occurrence of wheals (and, in about half of cases, angioedema) for more than 6 weeks. These are rather frequent conditions that may severely affect patients' quality of life and sometimes represent a challenge for doctors as well. The causes of chronic urticaria are still poorly defined, although there is growing evidence that different biologic systems including immunity, inflammation, and coagulation may take part in the pathomechanism eventually leading to mast cell and basophil degranulation and hence to wheal formation. This review will discuss the main findings that are (slowly) shedding light on the pathogenesis of this disorder.
PubMed: 28751972
DOI: 10.12688/f1000research.11546.1 -
Frontiers in Immunology 2020Ticks are blood-sucking arthropods of great importance in the medical and veterinary fields worldwide. They are considered second only to mosquitos as vectors of... (Review)
Review
Ticks are blood-sucking arthropods of great importance in the medical and veterinary fields worldwide. They are considered second only to mosquitos as vectors of pathogenic microorganisms that can cause serious infectious disorders, such as Lyme borreliosis and tick-borne encephalitis. Hard () ticks feed on host animals for several days and inject saliva together with pathogens to hosts during blood feeding. Some animal species can acquire resistance to blood-feeding by ticks after a single or repeated tick infestation, resulting in decreased weights and numbers of engorged ticks or the death of ticks in subsequent infestations. Importantly, this acquired tick resistance (ATR) can reduce the risk of pathogen transmission from pathogen-infected ticks to hosts. This is the basis for the development of tick antigen-targeted vaccines to forestall tick infestation and tick-borne diseases. Accumulation of basophils is detected in the tick re-infested skin lesion of animals showing ATR, and the ablation of basophils abolishes ATR in mice and guinea pigs, illustrating the critical role for basophils in the expression of ATR. In this review article, we provide a comprehensive overview of recent advances in our understanding of the cellular and molecular mechanisms responsible for the development and manifestation of ATR, with a particular focus on the role of basophils.
Topics: Animals; Basophils; Histamine; Histamine Release; Host-Pathogen Interactions; Humans; Immunoglobulin E; Immunologic Memory; Insect Bites and Stings; Saliva; Skin; Tick-Borne Diseases; Ticks; Vaccination; Vaccines
PubMed: 33154758
DOI: 10.3389/fimmu.2020.601504 -
International Journal of Molecular... Aug 2023Anaphylaxis is a life-threatening or even fatal systemic hypersensitivity reaction. The incidence of anaphylaxis has risen at an alarming rate in the past decades in the... (Review)
Review
Anaphylaxis is a life-threatening or even fatal systemic hypersensitivity reaction. The incidence of anaphylaxis has risen at an alarming rate in the past decades in the majority of countries. Generally, the most common causes of severe or fatal anaphylaxis are medication, foods and venoms. Anaphylactic reactions are characterized by the activation of mast cells and basophils and the release of mediators. These cells express a variety of receptors that enable them to respond to a wide range of stimulants. Most studies of anaphylaxis focus on IgE-dependent reactions. The mast cell has long been regarded as the main effector cell involved in IgE-mediated anaphylaxis. This paper reviews IgE-independent anaphylaxis, with special emphasis on mast cells, basophils, anaphylactic mediators, risk factors, triggers, and management.
Topics: Humans; Anaphylaxis; Mast Cells; Basophils; Central Nervous System Stimulants; Immunoglobulin E
PubMed: 37628983
DOI: 10.3390/ijms241612802