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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 -
The Journal of Allergy and Clinical... Jan 2023Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear.
OBJECTIVE
We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD.
METHODS
As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence.
RESULTS
Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings.
CONCLUSIONS
SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.
Topics: Adult; Animals; Humans; Child; Dermatitis, Atopic; Quality of Life; Bayes Theorem; Desensitization, Immunologic; Pyroglyphidae; Hypersensitivity; Asthma; Allergens; Sublingual Immunotherapy; Dermatophagoides pteronyssinus; Eczema
PubMed: 36191689
DOI: 10.1016/j.jaci.2022.09.020 -
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 -
Molecular Immunology Jun 2023House dust mite (HDM) allergy belongs to the most important allergies and affects approximately 65-130 million people worldwide. Additionally, untreated HDM allergy may... (Review)
Review
House dust mite (HDM) allergy belongs to the most important allergies and affects approximately 65-130 million people worldwide. Additionally, untreated HDM allergy may lead to the development of severe disease manifestations such as atopic dermatitis or asthma. Diagnosis and immunotherapy of HDM allergic patients are well established but are often hampered by the use of mite extracts that are of bad quality and lack important allergens. The use of individual allergens seems to be a promising alternative to natural allergen extracts, since they represent well-defined components that can easily be produced and quantified. However, a thorough characterization of the individual allergens is required to determine their clinical relevance and to identify those allergens that are required for correct diagnosis of HDM allergy and for successful immunotherapy. This review gives an update on the individual HDM allergens and their benefits for diagnosis and immunotherapy of HDM allergic patients.
Topics: Humans; Animals; Dust Mite Allergy; Hypersensitivity; Allergens; Immunotherapy; Antigens, Dermatophagoides; Pyroglyphidae
PubMed: 37119758
DOI: 10.1016/j.molimm.2023.04.008 -
Science Immunology Oct 2023Despite robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and the interplay between inflammatory and...
Despite robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and the interplay between inflammatory and neurosensory pathways remain unmapped. Here, we examined the consequences of disrupting and its receptor in a mouse model of house dust mite (HDM)-induced allergic dermatitis. -deficient mice displayed a deficit in HDM dermatitis-associated scratching, consistent with its well-established role as a pruritogen. In contrast, deficiency increased the number and proportion of cutaneous type 2 cytokine-producing CD4 T cells and serum IgE in response to HDM. Furthermore, monocytes and macrophages capable of fueling a feedforward type 2 inflammatory loop were selectively enriched in -deficient HDM dermatitis skin. Thus, IL-31 is not strictly a proinflammatory cytokine but rather an immunoregulatory factor that limits the magnitude of type 2 inflammatory responses in skin. Our data support a model wherein IL-31 activation of IL31RA pruritoceptors triggers release of calcitonin gene-related protein (CGRP), which can mediate neurogenic inflammation, inhibit CD4 T cell proliferation, and reduce T cell production of the type 2 cytokine IL-13. Together, these results illustrate a previously unrecognized neuroimmune pathway that constrains type 2 tissue inflammation in the setting of chronic cutaneous allergen exposure and may explain paradoxical dermatitis flares in atopic patients treated with anti-IL31RA therapy.
Topics: Animals; Mice; Cytokines; Dermatitis, Atopic; Immunity; Neurogenic Inflammation; Pyroglyphidae; Skin; Interleukins
PubMed: 37831760
DOI: 10.1126/sciimmunol.abi6887 -
Cellular & Molecular Immunology Feb 2022We sought to examine the regulatory effect of Meteorin-β (Metrnβ)/Meteorin like (Metrnl)/IL-41 on lung inflammation in allergic asthma. We found that Metrnβ was...
We sought to examine the regulatory effect of Meteorin-β (Metrnβ)/Meteorin like (Metrnl)/IL-41 on lung inflammation in allergic asthma. We found that Metrnβ was elevated significantly in asthmatic patients and in mice with allergic asthma induced by house dust mite (HDM) extract. Upon exposure to HDM, Metrnβ was secreted predominantly by airway epithelial cells and inflammatory cells, including macrophages and eosinophils. The increased Metrnβ effectively blocked the development of airway hyperreactivity (AHR) and decreased inflammatory cell airway infiltration and type 2 cytokine production, which was associated with downregulated DC-mediated adaptive immune responses. Moreover, Metrnβ impaired the maturation and function of bone marrow-derived dendritic cells in vitro. Asthmatic mice adoptively transferred with dendritic cells isolated from Metrnβ-treated allergic mice displayed decreased AHR, airway inflammation, and lung injury. Metrnβ also displayed anti-inflammatory properties in immunodeficient SCID mice with allergic asthma and in in vitro 3D ALI airway models. Moreover, blockade of Metrnβ by anti-Metrnβ antibody treatment promoted the development of allergic asthma. These results revealed the unappreciated protective roles of Metrnβ in alleviating DC-mediated Th2 inflammation in allergic asthma, providing the novel treatment strategy of therapeutic targeting of Metrnβ in allergic asthma.
Topics: Allergens; Animals; Asthma; Dendritic Cells; Disease Models, Animal; Humans; Inflammation; Mice; Mice, SCID; Pyroglyphidae; Th2 Cells
PubMed: 34848868
DOI: 10.1038/s41423-021-00803-8 -
Frontiers in Immunology 2021Inhaled allergens promote inflammatory response, tissue damage, and airway hyperresponsiveness in the lungs, leading to allergic asthma. NLRP3, as an immune sensor of...
Inhaled allergens promote inflammatory response, tissue damage, and airway hyperresponsiveness in the lungs, leading to allergic asthma. NLRP3, as an immune sensor of infections and cellular stress, is associated with the development and exacerbation of asthma. However, the mechanism by which NLRP3 affects asthma requires further investigation. Here, we showed that inhaled house dust mite (HDM) promotes NLRP3 inflammasome activation in the lungs and specifically induces the maturation of caspase-1 and IL-1β in alveolar macrophages (AMs). Using -mutant mice, we found that NLRP3 promotes the inflammatory response and pathogenesis in HDM-induced allergic asthma in an inflammasome-dependent manner. Treatment with RRx-001, an NLRP3 inhibitor, significantly reduced inflammatory cell infiltration and mucus secretion in the airway. Our results showed that NLRP3 in myeloid cells promoted the development and progression of allergic asthma in an inflammasome-dependent manner. Small molecules targeting the NLRP3 inflammasome may provide new treatment options for this disease.
Topics: Allergens; Animals; Asthma; Biomarkers; Disease Models, Animal; Disease Susceptibility; Immunohistochemistry; Inflammasomes; Macrophage Activation; Macrophages, Alveolar; Mice; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroglyphidae
PubMed: 34413860
DOI: 10.3389/fimmu.2021.718779 -
Immunity Jul 2019Naive CD4 T cells differentiate into functionally diverse T helper (Th) cell subsets. Th2 cells play a pathogenic role in asthma, yet a clear picture of their...
Naive CD4 T cells differentiate into functionally diverse T helper (Th) cell subsets. Th2 cells play a pathogenic role in asthma, yet a clear picture of their transcriptional profile is lacking. We performed single-cell RNA sequencing (scRNA-seq) of T helper cells from lymph node, lung, and airways in the house dust mite (HDM) model of allergic airway disease. scRNA-seq resolved transcriptional profiles of naive CD4 T, Th1, Th2, regulatory T (Treg) cells, and a CD4 T cell population responsive to type I interferons. Th2 cells in the airways were enriched for transcription of many genes, including Cd200r1, Il6, Plac8, and Igfbp7, and their mRNA profile was supported by analysis of chromatin accessibility and flow cytometry. Pathways associated with lipid metabolism were enriched in Th2 cells, and experiments with inhibitors of key metabolic pathways supported roles for glucose and lipid metabolism. These findings provide insight into the differentiation of pathogenic Th2 cells in the context of allergy.
Topics: Animals; Antigens, Dermatophagoides; Asthma; Disease Models, Animal; Humans; Lipid Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Orexin Receptors; Pyroglyphidae; Respiratory Hypersensitivity; Respiratory System; Sequence Analysis, RNA; Single-Cell Analysis; T-Lymphocyte Subsets; Th2 Cells; Transcriptome
PubMed: 31231035
DOI: 10.1016/j.immuni.2019.05.014 -
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