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Allergy Jun 2021Basophils and mast cells contribute to the development of allergic reactions. Whereas these mature effector cells are extensively studied, the differentiation...
BACKGROUND
Basophils and mast cells contribute to the development of allergic reactions. Whereas these mature effector cells are extensively studied, the differentiation trajectories from hematopoietic progenitors to basophils and mast cells are largely uncharted at the single-cell level.
METHODS
We performed multicolor flow cytometry, high-coverage single-cell RNA sequencing analyses, and cell fate assays to chart basophil and mast cell differentiation at single-cell resolution in mouse.
RESULTS
Analysis of flow cytometry data reconstructed a detailed map of basophil and mast cell differentiation, including a bifurcation of progenitors into two specific trajectories. Molecular profiling and pseudotime ordering of the single cells revealed gene expression changes during differentiation. Cell fate assays showed that multicolor flow cytometry and transcriptional profiling successfully predict the bipotent phenotype of a previously uncharacterized population of peritoneal basophil-mast cell progenitors.
CONCLUSIONS
A combination of molecular and functional profiling of bone marrow and peritoneal cells provided a detailed road map of basophil and mast cell development. An interactive web resource was created to enable the wider research community to explore the expression dynamics for any gene of interest.
Topics: Animals; Basophils; Bone Marrow Cells; Cell Differentiation; Mast Cells; Mice; Stem Cells
PubMed: 33078414
DOI: 10.1111/all.14633 -
Frontiers in Immunology 2020Food allergy is a major health issue, affecting the lives of 8% of U.S. children and their families. There is an urgent need to identify the environmental and endogenous... (Review)
Review
Food allergy is a major health issue, affecting the lives of 8% of U.S. children and their families. There is an urgent need to identify the environmental and endogenous signals that induce and sustain allergic responses to ingested allergens. Acute reactions to foods are triggered by the activation of mast cells and basophils, both of which release inflammatory mediators that lead to a range of clinical manifestations, including gastrointestinal, cutaneous, and respiratory reactions as well as systemic anaphylaxis. Both of these innate effector cell types express the high affinity IgE receptor, FcϵRI, on their surface and are armed for adaptive antigen recognition by very-tightly bound IgE antibodies which, when cross-linked by polyvalent allergen, trigger degranulation. These cells also express inhibitory receptors, including the IgG Fc receptor, FcγRIIb, that suppress their IgE-mediated activation. Recent studies have shown that natural resolution of food allergies is associated with increasing food-specific IgG levels. Furthermore, oral immunotherapy, the sequential administration of incrementally increasing doses of food allergen, is accompanied by the strong induction of allergen-specific IgG antibodies in both human subjects and murine models. These can deliver inhibitory signals FcγRIIb that block IgE-induced immediate food reactions. In addition to their role in mediating immediate hypersensitivity reactions, mast cells and basophils serve separate but critical functions as adjuvants for type 2 immunity in food allergy. Mast cells and basophils, activated by IgE, are key sources of IL-4 that tilts the immune balance away from tolerance and towards type 2 immunity by promoting the induction of Th2 cells along with the innate effectors of type 2 immunity, ILC2s, while suppressing the development of regulatory T cells and driving their subversion to a pathogenic pro-Th2 phenotype. This adjuvant effect of mast cells and basophils is suppressed when inhibitory signals are delivered by IgG antibodies signaling FcγRIIb. This review summarizes current understanding of the immunoregulatory effects of mast cells and basophils and how these functions are modulated by IgE and IgG antibodies. Understanding these pathways could provide important insights into innovative strategies for preventing and/or reversing food allergy in patients.
Topics: Allergens; Animals; Basophils; Desensitization, Immunologic; Food Hypersensitivity; Humans; Immunoglobulin E; Immunoglobulin G; Mast Cells; Phenotype; Receptors, Fc; Signal Transduction; Treatment Outcome
PubMed: 33362785
DOI: 10.3389/fimmu.2020.603050 -
Allergology International : Official... Jul 2023Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to... (Review)
Review
Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to allergen-induced skin reactions supports that skin mast cell IgE receptor activation is also involved in CSU. Accumulating evidence also supports a role for blood basophils in disease expression. Blood basopenia is noted in active CSU disease with the recruitment of blood basophils to skin lesion sites. Blood basophils further display altered IgE receptor mediated degranulation patterns in two phenotypes that improve in remission. In active CSU subjects, changes in IgE receptor signaling molecule expression levels accompany the altered degranulation function in blood basophils. The success of therapies targeting IgE in CSU patients have also shown that altered blood basophil phenotypes and enumeration have potential use as a disease biomarker.
Topics: Humans; Basophils; Receptors, IgE; Chronic Disease; Urticaria; Chronic Urticaria
PubMed: 37221123
DOI: 10.1016/j.alit.2023.05.001 -
Nature Communications May 2023Basophils are the rarest granulocytes and are recognized as critical cells for type 2 immune responses. However, their differentiation pathway remains to be fully...
Basophils are the rarest granulocytes and are recognized as critical cells for type 2 immune responses. However, their differentiation pathway remains to be fully elucidated. Here, we assess the ontogenetic trajectory of basophils by single-cell RNA sequence analysis. Combined with flow cytometric and functional analyses, we identify c-KitCLEC12A pre-basophils located downstream of pre-basophil and mast cell progenitors (pre-BMPs) and upstream of CLEC12A mature basophils. The transcriptomic analysis predicts that the pre-basophil population includes previously-defined basophil progenitor (BaP)-like cells in terms of gene expression profile. Pre-basophils are highly proliferative and respond better to non-IgE stimuli but less to antigen plus IgE stimulation than do mature basophils. Although pre-basophils usually remain in the bone marrow, they emerge in helminth-infected tissues, probably through IL-3-mediated inhibition of their retention in the bone marrow. Thus, the present study identifies pre-basophils that bridge the gap between pre-BMPs and mature basophils during basophil ontogeny.
Topics: Basophils; Transcriptome; Cell Differentiation; Receptor Protein-Tyrosine Kinases; Gene Expression Profiling
PubMed: 37202383
DOI: 10.1038/s41467-023-38356-1 -
Frontiers in Immunology 2020Basophil activation tests (BATs) can closely monitor, , a patient's propensity to develop type I hypersensitivity reactions. Because of their high specificity and... (Review)
Review
Basophil activation tests (BATs) can closely monitor, , a patient's propensity to develop type I hypersensitivity reactions. Because of their high specificity and sensitivity, BATs have become promising diagnostic tools, especially in cases with equivocal clinical histories, skin prick test results, and/or levels of specific IgE to allergen extracts. BATs also are useful as tools for monitoring the effects of treatment, since oral immunotherapy (OIT) studies report a diminution in patients' basophil responsiveness over the course of OIT. This review will discuss the BAT findings obtained before, during, and after OIT for food allergy. We will mainly focus on the association of basophil responsiveness, and alterations in basophil surface markers, with clinical outcomes and other clinical features, such as blood levels of specific IgG and IgE antibodies. The detailed analysis of these correlations will ultimately facilitate the use of BATs, along with other blood biomarkers, to differentiate short-term desensitization versus sustained unresponsiveness and to improve treatment protocols. Given the critical anatomic location of mast cells adjacent to the many IgE plasma cells found in the gastrointestinal tissues of allergic individuals, we will also discuss the role of gastrointestinal mast cells in manifestations of food allergies.
Topics: Administration, Oral; Allergens; Basophil Degranulation Test; Basophils; Biomarkers; Cell Degranulation; Desensitization, Immunologic; Food Hypersensitivity; Humans; Immunoglobulin E; Immunoglobulin G; Mast Cells; Predictive Value of Tests; Skin Tests; Treatment Outcome
PubMed: 33381123
DOI: 10.3389/fimmu.2020.602660 -
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 -
Seminars in Immunopathology Sep 2016Basophils and mast cells have long been known to play critical roles in allergic disease and in immunity against parasitic infection. Accumulated evidence also supports... (Review)
Review
Basophils and mast cells have long been known to play critical roles in allergic disease and in immunity against parasitic infection. Accumulated evidence also supports that basophils and mast cells have important roles in immune regulations, host defense against bacteria and viruses, and autoimmune diseases. However, origin and molecular regulation of basophil and mast cell differentiation remain incompletely understood. In this review, we focus on recent advances in the understanding of origin and molecular regulation of mouse and human basophil and mast cell development. A more complete understanding of how basophils and mast cells develop at the molecular level will lead to development of interventions that are more effective in achieving long-term success.
Topics: Animals; Basophils; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Cell Lineage; Gene Expression Regulation; Granulocyte-Macrophage Progenitor Cells; Hematopoiesis; Humans; Mast Cells; Mice; Microphthalmia-Associated Transcription Factor; Organ Specificity; Protein Binding; Transcription Factors; Transcription, Genetic
PubMed: 27126100
DOI: 10.1007/s00281-016-0562-4 -
Frontiers in Immunology 2020Basophils were identified in human peripheral blood by Paul Ehrlich over 140 years ago. Human basophils represent <1% of peripheral blood leukocytes. During the last... (Review)
Review
Basophils were identified in human peripheral blood by Paul Ehrlich over 140 years ago. Human basophils represent <1% of peripheral blood leukocytes. During the last decades, basophils have been described also in mice, guinea pigs, rabbits, and monkeys. There are many similarities, but also several immunological differences between human and mouse basophils. There are currently several strains of mice with profound constitutive or inducible basophil deficiency useful to prove that these cells have specific roles . However, none of these mice are solely and completely devoid of all basophils. Therefore, the relevance of these findings to humans remains to be established. It has been known for some time that basophils have the propensity to migrate into the site of inflammation. Recent observations indicate that tissue resident basophils contribute to lung development and locally promote M2 polarization of macrophages. Moreover, there is increasing evidence that lung-resident basophils exhibit a specific phenotype, different from circulating basophils. Activated human and mouse basophils synthesize restricted and distinct profiles of cytokines. Human basophils produce several canonical (e.g., VEGFs, angiopoietin 1) and non-canonical (i.e., cysteinyl leukotriene C) angiogenic factors. Activated human and mouse basophils release extracellular DNA traps that may have multiple effects in cancer. Hyperresponsiveness of basophils has been demonstrated in patients with JAK2-positive polycythemia vera. Basophils are present in the immune landscape of human lung adenocarcinoma and pancreatic cancer and can promote inflammation-driven skin tumor growth. The few studies conducted thus far using different models of basophil-deficient mice have provided informative results on the roles of these cells in tumorigenesis. Much more remains to be discovered before we unravel the hitherto mysterious roles of basophils in human and experimental cancers.
Topics: Angiogenesis Inducing Agents; Animals; Basophils; Carcinogenesis; Humans; Macrophages; Neoplasms
PubMed: 33013885
DOI: 10.3389/fimmu.2020.02103 -
Current Allergy and Asthma Reports Nov 2018The basophil activation test (BAT) using flow cytometry has supplanted traditional methods of measuring basophil degranulation using histamine and other mediator... (Review)
Review
PURPOSE OF REVIEW
The basophil activation test (BAT) using flow cytometry has supplanted traditional methods of measuring basophil degranulation using histamine and other mediator release, and can be used for clinical applications as well as to explore the immune mechanisms of effector cell response to allergen. This review discusses the advancements made in clinical, diagnostic and laboratory research of allergy utilizing an ever-evolving BAT.
RECENT FINDINGS
Being an in vitro surrogate of the allergic reaction that happens in vivo in the sick patient, the BAT can be used to support the diagnosis of various allergic conditions, such as food, drug, respiratory and insect venom allergies, and the assessment of clinical response to allergen-specific immunotherapy and other immunomodulatory treatments. The BAT can also be used for research purposes to explore the mechanisms of allergy and tolerance at the level of the basophil, for instance by manipulating IgE and IgG and their receptors and by studying intracellular signalling cascade in response to allergen. This review covers the applications of the BAT to the clinical management of allergic patients and the increased understanding of the mechanisms of immune response to allergens as well as technological advancements made in recent years.
Topics: Basophils; Cell Degranulation; Humans; Hypersensitivity; Immunomodulation
PubMed: 30430289
DOI: 10.1007/s11882-018-0831-5 -
Current Allergy and Asthma Reports Jul 2016We review basophil testing by flow cytometry with an emphasis on advantages and disadvantages. (Review)
Review
PURPOSE OF REVIEW
We review basophil testing by flow cytometry with an emphasis on advantages and disadvantages.
RECENT FINDINGS
There are many tools available to assess the presence and severity of allergic diseases in patients. For 50 years, peripheral blood basophils have been used as tools to study these diseases. It is a very accessible cell that binds IgE antibody and secretes the classical mediators responsible for the symptoms of allergic reactions. In the last decade, an even more accessible methodology, using flow cytometry, has been developed to enhance the ability to use basophils for both mechanistic and clinical diagnostics. Basophil testing has been included in diagnostics for different forms of allergies as well as to monitor disease status. A variety of studies have begun to establish both precise methods and their clinical relevance for disease diagnosis, but there remain some important questions on how to take optimal advantage of the behaviours of basophils.
Topics: Basophils; Flow Cytometry; Humans; Hypersensitivity
PubMed: 27411319
DOI: 10.1007/s11882-016-0633-6