-
The Journal of Allergy and Clinical... 2018It has been 50 years since the dust mite was first appreciated to be a major source of allergen in house dust, and by extension a key trigger of allergic respiratory... (Review)
Review
It has been 50 years since the dust mite was first appreciated to be a major source of allergen in house dust, and by extension a key trigger of allergic respiratory disease. Since that time a number of protein allergens have been identified and characterized, mainly from mite feces, and standardized mite extracts and IgE assays have been developed. Insights into the lifecycle of dust mites and aspects of mite allergen biology have shed light on the mechanisms that lead to respiratory disease and to the development of interventions that can minimize dust mite allergen exposure. It is now clear that dust mite allergy is a key contributor to asthma in many parts of the world, and that long-term avoidance can be effective for preventing sensitization and minimizing the development and severity of respiratory disease. Here, we discuss the evidence linking dust mites with respiratory disease, outline studies that support the efficacy of home environmental interventions, and highlight practical methods that have been shown to be effective as part of a multifaceted approach to dust mite avoidance.
Topics: Air Pollution, Indoor; Allergy and Immunology; Animals; Antigens, Dermatophagoides; Asthma; Environmental Exposure; History, 20th Century; History, 21st Century; Humans; Hypersensitivity; Immunoglobulin E; Life Cycle Stages; Lung Diseases; Pyroglyphidae; United States
PubMed: 29310755
DOI: 10.1016/j.jaip.2017.10.003 -
Annals of Allergy, Asthma & Immunology... May 2018To provide a comprehensive overview of common school exposures and the association between school exposures and pediatric asthma morbidity. (Review)
Review
OBJECTIVE
To provide a comprehensive overview of common school exposures and the association between school exposures and pediatric asthma morbidity.
DATA SOURCES
A comprehensive literature review was performed using PubMed.
STUDY SELECTIONS
Full-length, peer-reviewed studies published in English were considered for review. In vivo, in vitro, and animal studies were excluded. Studies of school exposure to cockroach, mouse, dust mite, dog, cat, molds, pollution, and endotoxin associated with asthma and asthma morbidity were considered.
RESULTS
The current literature establishes an association between school exposure and pediatric asthma morbidity. There is a need for ongoing research to evaluate the effects of school-based environmental interventions on asthma morbidity.
CONCLUSION
It is evident that the indoor school environment is a significant reservoir of allergens, molds, pollutants, and endotoxin and that there is an association between school exposure and pediatric asthma morbidity. School-based interventions have the potential for substantial individual, community, and public health benefit. It is important that researchers continue to study the health effects associated with school exposures and assess cost-effectiveness of multifaceted school-based interventions.
Topics: Adolescent; Air Pollution, Indoor; Allergens; Animals; Asthma; Cats; Child; Child, Preschool; Cockroaches; Dogs; Endotoxins; Environmental Exposure; Fungi; Humans; Immunoglobulin E; Mice; Primary Prevention; Pyroglyphidae; Schools; Students
PubMed: 29407419
DOI: 10.1016/j.anai.2018.01.028 -
The Journal of Allergy and Clinical... Jun 2022Infectious agents can reprogram or "train" macrophages and their progenitors to respond more readily to subsequent insults. However, whether such an inflammatory memory...
BACKGROUND
Infectious agents can reprogram or "train" macrophages and their progenitors to respond more readily to subsequent insults. However, whether such an inflammatory memory exists in type 2 inflammatory conditions such as allergic asthma was not known.
OBJECTIVE
We sought to decipher macrophage-trained immunity in allergic asthma.
METHODS
We used a combination of clinical sampling of house dust mite (HDM)-allergic patients, HDM-induced allergic airway inflammation in mice, and an in vitro training setup to analyze persistent changes in macrophage eicosanoid, cytokine, and chemokine production as well as the underlying metabolic and epigenetic mechanisms. Transcriptional and metabolic profiles of patient-derived and in vitro trained macrophages were assessed by RNA sequencing or metabolic flux analysis and liquid chromatography-tandem mass spectrometry analysis, respectively.
RESULTS
We found that macrophages differentiated from bone marrow or blood monocyte progenitors of HDM-allergic mice or asthma patients show inflammatory transcriptional reprogramming and excessive mediator (TNF-α, CCL17, leukotriene, PGE, IL-6) responses upon stimulation. Macrophages from HDM-allergic mice initially exhibited a type 2 imprint, which shifted toward a classical inflammatory training over time. HDM-induced allergic airway inflammation elicited a metabolically activated macrophage phenotype, producing high amounts of 2-hydroxyglutarate (2-HG). HDM-induced macrophage training in vitro was mediated by a formyl peptide receptor 2-TNF-2-HG-PGE/PGE receptor 2 axis, resulting in an M2-like macrophage phenotype with high CCL17 production. TNF blockade by etanercept or genetic ablation of Tnf in myeloid cells prevented the inflammatory imprinting of bone marrow-derived macrophages from HDM-allergic mice.
CONCLUSION
Allergen-triggered inflammation drives a TNF-dependent innate memory, which may perpetuate and exacerbate chronic type 2 airway inflammation and thus represents a target for asthma therapy.
Topics: Animals; Asthma; Dermatophagoides pteronyssinus; Disease Models, Animal; Humans; Hypersensitivity; Inflammation; Macrophages; Mice; Prostaglandins E; Pyroglyphidae
PubMed: 34974067
DOI: 10.1016/j.jaci.2021.11.026 -
Cells May 2020Asthma is an important issue not only in health but also in economics worldwide. Therefore, asthma animal models have been frequently used to understand the pathogenesis... (Review)
Review
Asthma is an important issue not only in health but also in economics worldwide. Therefore, asthma animal models have been frequently used to understand the pathogenesis of asthma. Recently, in addition to acquired immunity, innate immunity has also been thought to be involved in asthma. Among innate immune cells, group 2 innate lymphoid cells (ILC2s) have been considered to be crucial for eosinophilic airway inflammation by releasing T helper 2 cytokines. Moreover, house dust mites (HDMs) belonging to group 1 act on airway epithelial cells not only as allergens but also as cysteine proteases. The production of interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP) from airway epithelial cells was induced by the protease activity of HDMs. These cytokines activate ILC2s, and activated ILC2s produce IL-5, IL-9, IL-13, and amphiregulin. Hence, the HDM-induced asthma mouse model greatly contributes to understanding asthma pathogenesis. In this review, we highlight the relationship between ILC2s and the HDM in the asthma mouse model to help researchers and clinicians not only choose a proper asthma mouse model but also to understand the molecular mechanisms underlying HDM-induced asthma.
Topics: Animals; Aspergillus fumigatus; Asthma; Disease Models, Animal; Humans; Immunity, Innate; Lymphocytes; Mice; Ovalbumin; Pyroglyphidae
PubMed: 32397396
DOI: 10.3390/cells9051178 -
Proceedings of the National Academy of... Jan 2021Exaggerated airway hyperresponsiveness and inflammation are hallmarks of asthma, and lipopolysaccharide (LPS) exposure is linked to the severity of the disease and...
Exaggerated airway hyperresponsiveness and inflammation are hallmarks of asthma, and lipopolysaccharide (LPS) exposure is linked to the severity of the disease and steroid resistance. To investigate the mechanisms underlying asthma exacerbation, we established a mouse model of LPS-induced steroid-resistant exacerbation on the background of house dust mite (HDM)-induced asthma to profile the immune cells in lung by using single-cell RNA deep sequencing. Twenty immune subsets were identified by their molecular and functional properties. Specific cell clusters of basophils, type 2 innate lymphoid cells (ILC2), and CD8 memory T cells were the predominant sources of interleukin (IL)-4 and IL-13 transcripts whose expressions were dexamethasone resistant. Production of IL-13 by these cells was validated by IL-13-reporter mice. Neutralization of IL-13 abolished HDM/LPS-induced airway hyperresponsiveness, airway inflammation, and decreased mucus hypersecretion. Furthermore, using Ingenuity Pathway Analysis systems, we identified canonical pathways and upstream regulators that regulate the activation of basophils, ILC2, and CD8 memory T cells. Our study provides mechanistic insights and an important reference resource for further understanding of the immune landscape during asthma exacerbation.
Topics: Animals; Asthma; Disease Progression; Interleukin-13; Interleukin-4; Leukocytes; Lipopolysaccharides; Lung; Mice, Inbred BALB C; Mononuclear Phagocyte System; Pyroglyphidae; Single-Cell Analysis; Transcriptome; Mice
PubMed: 33397719
DOI: 10.1073/pnas.2005590118 -
The Journal of Allergy and Clinical... 2018
Topics: Animals; Dermatophagoides pteronyssinus; Pyroglyphidae
PubMed: 30033927
DOI: 10.1016/j.jaip.2018.04.029 -
Respiratory Research Sep 2022Epithelial-mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of...
BACKGROUND
Epithelial-mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown. We aimed to explore the effect and mechanism of IL-24 on EMT and to verify whether IL-37 could alleviate IL-24-induced EMT in chronic asthma.
METHODS
BEAS-2B cells were exposed to IL-24, and cell migration was assessed by wound healing and Transwell assays. The expression of EMT-related biomarkers (E-cadherin, vimentin, and α-SMA) was evaluated after the cells were stimulated with IL-24 with or without IL-37. A murine asthma model was established by intranasal administration of house dust mite (HDM) extracts for 5 weeks, and the effects of IL-24 and IL-37 on EMT and airway remodeling were investigated by intranasal administration of si-IL-24 and rhIL-37.
RESULTS
We observed that IL-24 significantly enhanced the migration of BEAS-2B cells in vitro. IL-24 promoted the expression of the EMT biomarkers vimentin and α-SMA via the STAT3 and ERK1/2 pathways. In addition, we found that IL-37 partially reversed IL-24-induced EMT in BEAS-2B cells by blocking the ERK1/2 and STAT3 pathways. Similarly, the in vivo results showed that IL-24 was overexpressed in the airway epithelium of an HDM-induced chronic asthma model, and IL-24 silencing or IL-37 treatment could reverse EMT biomarker expression.
CONCLUSIONS
Overall, these findings indicated that IL-37 mitigated HDM-induced airway remodeling by inhibiting IL-24-mediated EMT via the ERK1/2 and STAT3 pathways, thereby providing experimental evidence for IL-24 as a novel therapeutic target and IL-37 as a promising agent for treating severe asthma.
Topics: Airway Remodeling; Animals; Asthma; Bronchi; Epithelial-Mesenchymal Transition; Humans; Interleukin-1; Interleukins; Mice; Pyroglyphidae; Signal Transduction; Vimentin
PubMed: 36100847
DOI: 10.1186/s12931-022-02167-7 -
Human Vaccines & Immunotherapeutics Oct 2017House dust mite (HDM) is a predominant source of indoor aeroallergen worldwide, which induces allergic diseases including allergic rhinoconjunctivitis, allergic asthma,... (Review)
Review
House dust mite (HDM) is a predominant source of indoor aeroallergen worldwide, which induces allergic diseases including allergic rhinoconjunctivitis, allergic asthma, atopic eczema and other allergic skin diseases. Allergen specific immunotherapy (AIT) is the only potential disease-modifying treatment of HDM allergic subjects. However, AIT remains underused due to no universally accepted allergen standardization and a shortage of rigorous clinical studies to confirm safety and efficacy. With the effort of doctors and researchers in allergy field, efficacy, safety, standardization and strategy of AIT are being continuously developed. This review presents the updated research based on recently published trials and meta-analyses.
Topics: Allergens; Animals; Clinical Trials as Topic; Desensitization, Immunologic; Humans; Hypersensitivity; Meta-Analysis as Topic; Pyroglyphidae; Sublingual Immunotherapy
PubMed: 28853977
DOI: 10.1080/21645515.2017.1364823 -
Current Allergy and Asthma Reports Aug 2018The review provides insight into recent findings on bedroom allergen exposures, primarily focusing on pet, pest, and fungal exposures. (Review)
Review
PURPOSE OF REVIEW
The review provides insight into recent findings on bedroom allergen exposures, primarily focusing on pet, pest, and fungal exposures.
RECENT FINDINGS
Large-scale studies and improved exposure assessment technologies, including measurement of airborne allergens and of multiple allergens simultaneously, have extended our understanding of indoor allergen exposures and their impact on allergic disease. Practical, streamlined methods for exposure reduction have shown promise in some settings, and potential protective effects of early-life exposures have been further elucidated through the investigation of specific bacterial taxa. Advances in molecular allergology have yielded novel data on sensitization profiles and cross-reactivity. The role of indoor allergen exposures in allergic disease is complex and remains incompletely understood. Advancing our knowledge of various co-exposures, including the environmental and host microbiome, that interact with allergens in early life will be crucial for the development of efficacious interventions to reduce the substantial economic and social burden of allergic diseases including asthma.
Topics: Air Pollution, Indoor; Allergens; Animals; Environmental Exposure; Housing; Humans; Pyroglyphidae
PubMed: 30128784
DOI: 10.1007/s11882-018-0805-7 -
Journal of Leukocyte Biology Sep 2018
Topics: Allergens; Animals; Asthma; Inflammation; Pyroglyphidae
PubMed: 30106490
DOI: 10.1002/JLB.3CE0718-293