Abstract
Mast cells and their mediators have been implicated in the pathogenesis of asthma and allergy for decades. Allergic asthma is a complex chronic lung disease in which several different immune cells, genetic factors and environmental exposures influence the pathology. Mast cells are key players in the asthmatic response through secretion of a multitude of mediators with pro-inflammatory and airway-constrictive effects. Well-known mast cell mediators, such as histamine and bioactive lipids are responsible for many of the physiological effects observed in the acute phase of allergic reactions. The accumulation of mast cells at particular sites of the allergic lung is likely relevant to the asthma phenotype, severity and progression. Mast cells located in different compartments in the lung and airways have different characteristics and express different mediators. According to in vivo experiments in mice, lung mast cells develop from mast cell progenitors induced by inflammatory stimuli to migrate to the airways. Human mast cell progenitors have been identified in the blood circulation. A high frequency of circulating human mast cell progenitors may reflect ongoing pathological changes in the allergic lung. In allergic asthma, mast cells become activated mainly via IgE-mediated crosslinking of the high affinity receptor for IgE (FcεRI) with allergens. However, mast cells can also be activated by numerous other stimuli e.g. toll-like receptors and MAS-related G protein-coupled receptor X2. In this review, we summarize research with implications on the role and development of mast cells and their progenitors in allergic asthma and cover selected activation pathways and mast cell mediators that have been implicated in the pathogenesis. The review places an emphasis on describing mechanisms identified using in vivo mouse models and data obtained by analysis of clinical samples.
Highlights
The close relationship between mast cells and basophils was supported by a study showing that isolated single granulocytemonocyte progenitors (GMp) were capable of differentiating into both mast cells and basophils [8], which was recently confirmed by the demonstration of a basophil–mast cell progenitor (BMCp) population distinguished as Lin− Sca-1 − c-kit+ integrin β7hi CD16/32hi cells in mouse bone marrow using single cell RNA-sequencing [9]
This study suggested that Gata-1+ progenitors, defined as Lin− c-kithi CD41− cells with variable expression of CD16/32, have the capacity to differentiate into eosinophils, mast cells or basophils
In an acute OVA model of allergic airway inflammation, we found that mouse mast cell protease (mMCP)-6-deficient mice had reduced methacholine-induced airway hyperresponsiveness (AHR) but developed allergic airway inflammation [71]
Summary
Specialty section: This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology Mast cells and their mediators have been implicated in the pathogenesis of asthma and allergy for decades. Human mast cell progenitors have been identified in the blood circulation. A high frequency of circulating human mast cell progenitors may reflect ongoing pathological changes in the allergic lung. Mast cells become activated mainly via IgE-mediated crosslinking of the high affinity receptor for IgE (FcεRI) with allergens. We summarize research with implications on the role and development of mast cells and their progenitors in allergic asthma and cover selected activation pathways and mast cell mediators that have been implicated in the pathogenesis.
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