House Dust Mite Sensitization Research Articles

G-CSFR antagonism reduces mucosal injury and airways fibrosis in a virus-dependent model of severe asthma.

Asthma is a chronic disease that displays heterogeneous clinical and molecular features. A phenotypic subset of late-onset severe asthmatics has debilitating fixed airflow obstruction, increased neutrophilic inflammation and a history of pneumonia. Influenza A virus (IAV) is an important viral cause of pneumonia and asthmatics are frequently hospitalised during IAV epidemics. This study aims to determine whether antagonising granulocyte colony stimulating factor receptor (G-CSFR) prevents pneumonia-associated severe asthma. Mice were sensitised to house dust mite (HDM) to establish allergic airway inflammation and subsequently infected with IAV (HKx31/H3N2 subtype). A neutralising monoclonal antibody against G-CSFR was therapeutically administered. In IAV-infected mice with prior HDM sensitisation, a significant increase in airway fibrotic remodelling and airways hyper-reactivity was observed. A mixed granulocytic inflammatory profile consisting of neutrophils, macrophages and eosinophils was prominent and at a molecular level, G-CSF expression was significantly increased in HDMIAV-treated mice. Blockage of G-CSFR reduced neutrophilic inflammation in the bronchoalveolar and lungs by over 80% in HDMIAV-treated mice without altering viral clearance. Markers of NETosis (dsDNA and myeloperoxidase in bronchoalveolar), tissue injury (LDH activity in bronchoalveolar) and oedema (total bronchoalveolar-fluid protein) were also significantly reduced with anti-G-CSFR treatment. In addition, anti-G-CSFR antagonism significantly reduced bronchoalveolar gelatinase activity, active TFGβ lung levels, collagen lung expression, airways fibrosis and airways hyper-reactivity in HDMIAV-treated mice. We have shown that antagonising G-CSFR-dependent neutrophilic inflammation reduced pathological disruption of the mucosal barrier and airways fibrosis in an IAV-induced severe asthma model.

'Stay at home': Is it good or not for house dust mite sensitized children with respiratory allergies?

Lockdown was imposed for children for 75days in Turkey to limit the spread of COVID-19. During this period, children have to stay indoors, which might probably increase their exposures to indoor allergens and pollutants. Besides, reduced exposures to respiratory tract infections and outdoor pollutants might be favorable outcomes of this lockdown period. We evaluated the effects of the lockdown on house dust mite (HDM)-sensitized children with respiratory allergies. Three-month clinical and medication data of 165 mild-moderate asthmatic children with or without allergic rhinitis (AR), who were grouped according to their HDM sensitization status, were retrieved from patient records. Demographics, asthma control tests, nasal visual analog scores, and outdoor air quality monitoring data were used for assessments in comparisons with the same period in the previous year. Eighty-four patients had asthma, and 81 patients had asthma with AR. Sensitization to HDM was present in 61.8% of the children. Patients experienced reduced numbers of upper respiratory tract infections (P=.008) and reduced asthma exacerbations (P<.001) compared with the same period in the previous year. Asthma control tests were significantly improved (P<.001), and cumulative inhaled corticosteroid usages were significantly reduced (P<.001). Noteworthily, nasal symptoms were significantly worsened in HDM-sensitized asthmatics with AR (P<.001). This study highlighted that reduction in respiratory tract infections and outdoor pollution may play roles in asthma control and prevent exacerbations despite continuous indoor allergen exposure. Besides, worsening of nasal symptoms in HDM-sensitized asthmatics with AR implies the importance of indoor avoidance measures for AR control.

Mast cell-derived serotonin enhances methacholine-induced airway hyperresponsiveness in house dust mite-induced experimental asthma.

Airway hyperresponsiveness (AHR) is a feature of asthma in which airways are hyperreactive to stimuli causing extensive airway narrowing. Methacholine provocations assess AHR in asthma patients mainly by direct stimulation of smooth muscle cells. Using in vivo mouse models, mast cells have been implicated in AHR, but the mechanism behind has remained unknown. Cpa3Cre/+ mice, which lack mast cells, were used to assess the role of mast cells in house dust mite (HDM)-induced experimental asthma. Effects of methacholine in presence or absence of ketanserin were assessed on lung function and in lung mast cells in vitro. Airway inflammation, mast cell accumulation and activation, smooth muscle proliferation, and HDM-induced bronchoconstriction were evaluated. Repeated intranasal HDM sensitization induced allergic airway inflammation associated with accumulation and activation of lung mast cells. Lack of mast cells, absence of activating Fc-receptors, or antagonizing serotonin (5-HT)2A receptors abolished HDM-induced trachea contractions. HDM-sensitized mice lacking mast cells had diminished lung-associated 5-HT levels, reduced AHR and methacholine-induced airway contraction, while blocking 5-HT2A receptors in wild types eliminated AHR, implying that mast cells contribute to AHR by releasing 5-HT. Primary mouse and human lung mast cells express muscarinic M3 receptors. Mouse lung mast cells store 5-HT intracellularly, and methacholine induces release of 5-HT from lung-derived mouse mast cells and Ca2+ flux in human LAD-2 mast cells. Methacholine activates mast cells to release 5-HT, which by acting on 5-HT2A receptors enhances bronchoconstriction and AHR. Thus, M3-directed asthma treatments like tiotropium may also act by targeting mast cells.

Comparison of house dust mitesensitization profiles in allergic adults from Canada, Europe, South Africa and USA.

Sensitization to house dust mite (HDM) is a leading cause of allergic rhinitis and asthma. Despite more than 30 HDM-derived allergens having been identified to date, specific therapeutic approaches do not yet take into account the local sensitization profiles of patients. This study aimed to identify patterns of HDM sensitization in HDM-allergic adults living in distinct geographic areas, to inform the development of targeted diagnostic and therapeutic tools. Serum samples from 685 HDM-allergic subjects from Canada, Europe, South Africa, and the USA were tested for levels of IgE specific for 17 micro-arrayed HDM allergens by ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC) technology. The results confirmed significant geographical variability in sensitization patterns and levels of IgE. In all areas, the major sensitizers were the group 1 and group 2 allergens and Der p 23. Der p 23 was a frequent sensitizer: 64% of the subjects had IgE specific for Der p 23, and 2.3% were monosensitized to it. In South Africa, Der p 23 was the dominant HDM allergen (86% prevalence) and Der p 7 achieved major allergen status (56%). IgE sensitization to HDM was influenced by asthmatic status, levels of allergen exposure, age, race-ethnicity and smoking status, but not by BMI. Sensitization profiles to HDM allergens differ considerably among distinct geographic areas, with Der p 7 and Der p 23 being major sensitizers in South Africa. Such heterogeneity should be taken into account in the diagnosis and treatment of HDM-allergic patients.

House dust mite sensitization drives cross-reactive immune responses to homologous helminth proteins.

The establishment of type 2 responses driven by allergic sensitization prior to exposure to helminth parasites has demonstrated how tissue-specific responses can protect against migrating larval stages, but, as a consequence, allow for immune-mediated, parasite/allergy-associated morbidity. In this way, whether helminth cross-reacting allergen-specific antibodies are produced and play a role during the helminth infection, or exacerbate the allergic outcome awaits elucidation. Thus, the main objective of the study was to investigate whether house dust mite (HDM) sensitization triggers allergen-specific antibodies that interact with Ascaris antigens and mediate antibody-dependent deleterious effects on these parasites as well as, to assess the capacity of cross-reactive helminth proteins to trigger allergic inflammation in house dust mite presensitized mice. Here, we show that the sensitization with HDM-extract drives marked IgE and IgG1 antibody responses that cross-react with Ascaris larval antigens. Proteomic analysis of Ascaris larval antigens recognized by these HDM-specific antibodies identified Ascaris tropomyosin and enolase as the 2 major HDM homologues based on high sequence and structural similarity. Moreover, the helminth tropomyosin could drive Type-2 associated pulmonary inflammation similar to HDM following HDM tropomyosin sensitization. The HDM-triggered IgE cross-reactive antibodies were found to be functional as they mediated immediate hypersensitivity responses in skin testing. Finally, we demonstrated that HDM sensitization in either B cells or FcγRIII alpha-chain deficient mice indicated that the allergen driven cell-mediated larval killing is not antibody-dependent. Taken together, our data suggest that aeroallergen sensitization drives helminth reactive antibodies through molecular and structural similarity between HDM and Ascaris antigens suggesting that cross-reactive immune responses help drive allergic inflammation.

Analysis of the long-term efficacy and safety of subcutaneous immunotherapy for atopic dermatitis.

Introduction: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by severe pruritus and eczematous skin lesions. Subcutaneous immunotherapy (SCIT) refers to repeated contact with gradually increasing doses of allergen extracts, which improve patient tolerance to such allergens and controls, or reduces allergic symptoms. This study aimed to explore the long-term efficacy and safety of SCIT for patients with AD sensitized to house-dust mite (HDM). Methods: We conducted a retrospective analysis of 378 patients with HDM-sensitized AD. Among these patients, 164 received SCIT plus pharmacotherapy for 3 years (SCIT group) and the other 214 patients received only pharmacotherapy (non-SCIT group). The scoring atopic dermatitis (SCORAD) and pruritus visual analog scale (VAS) scores, laboratory test results, and adverse effects were recorded. Results: The SCORAD and pruritus VAS scores significantly decreased in the SCIT group. Also, the SCIT group showed higher reduction ratios of SCORAD and pruritus VAS scores than those observed in the non-SCIT group at 3 years after treatment initiation. The risk of development of new sensitization was higher in the non-SCIT group than in the SCIT group (relative risk 1.92 [95% confidence interval {CI}, 1.30-2.85]; p < 0.05). The eosinophil count of the participants significantly differed in the complete response (CR) group (p < 0.05) but not in the non-CR group (p = 0.098). However, the serum total immunoglobulin E value was not significantly reduced (p = 0.204). Of 8421 injections given to the patients, 231 injections (2.74%) showed adverse effects during the treatment period. Conclusion: Three years of SCIT can significantly reduce the severity and pruritus of moderate-to-severe AD with HDM sensitization. Patients who are multisensitized can also benefit from HDM SCIT. Patients can achieve long-term effects, such as prevention of neoallergen sensitization and inhibition of the allergy march.

IL-4 and IL-17 Are Required for House Dust Mite-Driven Airway Hyperresponsiveness in Autoimmune Diabetes-Prone Non-Obese Diabetic Mice.

Allergic asthma is characterized by airway inflammation with a Th2-type cytokine profile, hyper-IgE production, mucus hypersecretion, and airway hyperreactivity (AHR). It is increasingly recognized that asthma is a heterogeneous disease implicating complex immune mechanisms resulting in distinct endotypes observed in patients. In this study, we showed that non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, undergo more severe allergic asthma airway inflammation and AHR than pro-Th2 BALB/c mice upon house dust mite (HDM) sensitization and challenge. The use of IL-4-deficient NOD mice and the in vivo neutralization of IL-17 demonstrated that both IL-4 and IL-17 are responsible by the exacerbated airway inflammation and AHR observed in NOD mice. Overall, our findings indicate that autoimmune diabetes-prone NOD mice might become useful as a new HDM-induced asthma model to elucidate allergic dysimmune mechanisms involving Th2 and Th17 responses that could better mimic some asthmatic endoytpes.

House Dust Mite Sensitization is Associated with Resistance to Topical Therapy in Patients with Contact Dermatitis

House Dust Mite Sensitization is Associated with Resistance to Topical Therapy in Patients with Contact Dermatitis

Effect of house dust mite sublingual immunotherapy in patients with Atopic Dermatitis: a randomized, double-blind, placebo-controlled clinical trial

House dust mites (HDM) sensitization is often found in patients with atopic dermatitis (AD). We aimed to investigate the role of sublingual immunotherapy (SLIT) as adjuvant treatment for patients with AD allergic to HDM.

Seasonality of asthma exacerbation in children caused by respiratory virus infection and allergen sensitization

Purpose: Acute asthma exacerbations in children have seasonal variations and occur frequently in fall. Respiratory viral infections and environmental allergens are associated with asthma exacerbation. This study aimed to identify seasonal trends of asthma exac-erbation and the effects of respiratory viral infection and allergen sensitization on the seasonality of asthma exacerbation in children. Methods: Children under the age of 18 years who visited to the Emergency Department or hospitalized for acute asthma exacerba-tions from 2011 to 2019 were included. We reviewed medical records, including demographics, date of asthma exacerbation, results of respiratory virus and allergen sensitization, and they were analyzed to identify the seasonal trends of asthma exacerbation. Results: A total of 320 asthma exacerbations were included, with the highest frequency in fall. Human rhinovirus was positive in 64.7% and 60.0% in fall and spring exacerbations, respectively. House dust mite sensitization was highest in fall at 78.5%, while food sensitization was highest in spring at 76.9%. In patients who were sensitized to house dust mites or food allergens, respiratory viral infections further increased asthma exacerbation in fall and spring, respectively. Conclusion: Respiratory virus may be associated with asthma exacerbation in fall and spring. House dust mite and food sensitiza-tions may be associated with fall and spring asthma exacerbations by worsening the severity of asthma symptoms caused by respi-ratory viral infections. In childhood asthmatic patients with allergen sensitization, avoidance of sensitized allergens, prevention of viral infection, and more active treatment of viral infection may help prevent acute asthma exacerbations. (Allergy Asthma Respir Dis 2021;9:238-244)

Trajectories of early-onset rhinitis in the Singapore GUSTO mother-offspring cohort.

The natural history of childhood rhinitis is not well described. This study aimed to identify different rhinitis trajectories in early childhood and their predictors and allergic associations. Rhinitis symptoms were ascertained prospectively from birth until 6years using standardized questionnaires in 772 participants. Rhinitis was defined as one or more episodes of sneezing, runny and/or blocked nose >2weeks duration. Latent trajectories were identified using group-based modelling, and their predictive risk factors and allergic associations were examined. Three rhinitis trajectory groups were identified: 7.6% (n=59) were termed early transient rhinitis, 8.6% (n=66) late transient rhinitis, and 6.6% (n=51) persistent rhinitis. The remaining 77.2% (n=596) were classified as non-rhinitis/reference group. Early transient rhinitis subjects were more likely of Indian ethnicity, had siblings, reported childcare attendance, early wheezing and eczema in the first 3years of life. Late transient rhinitis was associated with antenatal exposure to smoking, higher maternal education levels, andwheezing at age 36-72months. Persistent rhinitis was associated with male gender, paternal and maternal history of atopy, eczema, and house dust mite sensitization. Risk factors for early transient rhinitis involve a combination of genetic and early environmental exposures, whereas late transient rhinitis may relate to maternal factors and early respiratory infections independent of atopy. In contrast, persistent rhinitis is strongly associated with atopic risk and likely represents the typical trajectory associated with allergic disorders. Allergic rhinitis symptoms may commence as early as the first year of life and may inform development of early interventive strategies.

Precision Medicine in House Dust Mite-Driven Allergic Asthma.

House dust mites (HDMs) are the allergenic sources most frequently involved in airway allergy. Nevertheless, not every sensitized patient develops respiratory symptoms upon exposure to HDM, and there is a clinical need to differentiate allergic asthmatics (AAs) from atopic non-allergic asthmatics with HDM sensitization. This differentiation sometimes requires in vivo provocations like the bronchial allergen challenge (BAC). Interestingly, recent data demonstrate that non-atopic patients with asthma can also develop positive BAC results. This novel phenotype has been termed local allergic asthma (LAA). The interest in identifying the allergic triggers of asthma resides in the possibility of administering allergen immunotherapy (AIT). AIT is a disease-modifying intervention, the clinical benefit of which persists after therapy discontinuation. Recently, new modalities of sublingual tablets of HDM immunotherapy registered as pharmaceutical products (HDM-SLIT tablets) have become commercially available. HDM-SLIT tablets have demonstrated a robust effect over critical asthma parameters (dose of inhaled corticosteroids, exacerbations, and safety), thus being recommended by international guidelines for patients with HDM-driven AA. In this review, we will summarize the current knowledge on the phenotype and endotype of HDM-driven AA, and LAA, address the difficulties for BAC implementation in the clinic, and discuss the effects of AIT in AA and LAA.

Sensitization rates to common inhaled allergens in Germany - increase and change patterns over the last 20 years.

Sensitization rates to aeroallergens are rising worldwide. The prevalence is increasing, especially in Western countries. We aimed to investigate (1) sensitization rates and (2) cross-sensitization patterns in skin prick tests (SPTs) for the most relevant inhaled allergens in central Germany over 20 years, adjusted for regional pollen counts. This monocentric study evaluated SPTs for tree pollen, grass pollen and house dust mites (HDMs) in 4,315 patients (including children) with suspected airway allergies, from 1998-2017. Sensitization rates to almost all aeroallergens have increased significantly over time, without relevant changes in regional pollen counts. Current sensitization rates in all our symptomatic patients were highest for grass (55.3%) and rye pollen (59.6%), with most pronounced increases in HDM sensitization over time (from 37.8% to the current figure of 50.1%). However, a low but consistent proportion of tree-sensitized patients (3.6-7.8%) showed isolated positive SPTs to alder and/or hazel pollen without sensitization to birch pollen. We demonstrate a significant rise in the total number of sensitized patients as well as increases in cross-sensitization between closely related allergens. Individuals with unusual mono-sensitization profiles to common inhaled allergens should be studied in more detail, since these patients are currently excluded from clinical trials for allergen immunotherapy.

Reduced allergic lung inflammation and airway responsiveness in mice lacking the cytoskeletal protein gelsolin.

Airway smooth muscle hyperresponsiveness associated with chronic airway inflammation leads to the typical symptoms of asthma including bronchoconstriction and wheezing. Asthma severity is associated with airway inflammation; therefore, reducing airway inflammation is an important therapeutic target. Gelsolin is an actin capping and severing protein that has been reported to be involved in modulation of the inflammatory response. Using mice genetically lacking gelsolin, we evaluated the role of gelsolin in the establishment of house dust mite (HDM) antigen-induced allergic lung inflammation. The genetic absence of gelsolin was found to be protective against HDM sensitization, resulting in reduced lung inflammation, inflammatory cytokines, and Muc5AC protein in bronchoalveolar lavage (BAL) fluid. The number of eosinophils, lymphocytes, and interstitial macrophages in the BAL were increased after HDM sensitization in wild-type mice but were attenuated in gelsolin-null mice. The observed attenuation of inflammation may be partly due to delayed migration of immune cells, because the reduced eosinophils in the BALs from gelsolin-null mice compared with controls occurred despite similar amounts of the chemoattractant eotaxin. Splenic T cells demonstrated similar proliferation rates, but ex vivo alveolar macrophage migration was delayed in gelsolin-null mice. In vivo, the reduced lung inflammation after HDM sensitization in gelsolin-null mice was associated with significantly diminished airway resistance to inhaled methacholine compared with HDM-treated wild-type mice. Our results suggest that modulation of gelsolin expression or function in selective inflammatory cell types that modulate allergic lung inflammation could be a therapeutic approach for asthma.

Cross-talk between airway and gut microbiome links to IgE responses to house dust mites in childhood airway allergies

A connection between airway and gut microbiota related to allergen exposure in childhood allergies was not well addressed. We aimed to identify the microbiota alterations in the airway and gut related to mite-specific IgE responses in young children with airway allergies. This study enrolled 60 children, including 38 mite-sensitized children (20 rhinitis and 18 asthma), and 22 non-mite-sensitized healthy controls. Microbiome composition analysis of the throat swab and stool samples was performed using bacterial 16S rRNA sequencing. An integrative analysis of the airway and stool microbial profiling associated with IgE reactions in childhood allergic rhinitis and asthma was examined. The Chao1 and Shannon indices in the airway were significantly lower than those in the stool. Additionally, an inverse association of the airway microbial diversity with house dust mite (HDM) sensitization and allergic airway diseases was noted. Fecal IgE levels were positively correlated with the serum Dermatophagoides pteronyssinus- and Dermatophagoides farinae-specific IgE levels. Airway Leptotrichia spp. related to asthma were strongly correlated with fecal Dorea and Ruminococcus spp., which were inversely associated with fecal IgE levels and risk of allergic rhinitis. Moreover, four airway genera, Campylobacter, Selenomonas, Tannerella, and Atopobium, were negatively correlated with both serum mite-specific and fecal IgE levels. Among them, the airway Selenomonas and Atopobium spp. were positively correlated with stool Blautia and Dorea spp. related to asthma and allergic rhinitis, respectively. In conclusion, airway microbial dysbiosis in response to HDM and its cross-talk with the gut microbial community is related to allergic airway diseases in early childhood.

Interleukin 25, thymic stromal lymphopoietin and house dust mites in pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the world. It is characterized by recurrent eczematous skin lesions, fluctuating course and chronic pruritus. Increasing evidence suggest that AD is more common in adults than previously thought. The disease is characterized by an impaired skin barrier, aberrant Th2-type cytokine production and intensive pruritus. Epithelial keratinocytes constitute the first physical, chemical and immunological barrier, classified as a part of the innate defense system. These keratinocytes secrete various factors, e.g. alarmins such as thymic stromal lymphopoietin (TSLP) and interleukin 25 (IL-25). Serum levels of substance P (SP) have been reported to be increased in patients with AD and correlated with itch intensity. Several previous studies reported a positive association between AD severity and house dust mites (HDM) sensitization. The aim of the study was to analyze IL-25, TSLP and SP concentrations in blood serum of adult patients with severe AD, depending on the degree of allergy to HDM. There were 31 adult AD patients enrolled into the study and a control group that consisted of 20 healthy subjects. AD was diagnosed on the basis of Hanifin and Rajka criteria. SCORing Atopic Dermatitis (SCORAD) and visual analogue (VAS) scores were used to assess the intensity of pruritus and blood content of specific IgE to HDM, as well as TSLP, IL-25 cytokines and SP was measured. Our study presents the evidence that IL-25 serum concentration is increased in patients with atopic dermatitis and this cytokine plays an important role in pathogenesis of this disease. HDM could stimulate the release of IL-25 which aggravates the disease severity. Our results corroborate previous findings on the role of TSLP in atopic dermatitis.

Sensitization to aeroallergens in an atopic population of Algiers (Algeria)

Aeroallergen sensitization is increasing worldwide. The optimal management of allergic disease requires the identification of the allergic sensitivities of the patient. The aim of the present study was to evaluate the profile of specific IgE reactivity of patients with clinically suspected allergic diseases seeking medical care in Algiers. The prevalence of 29 aeroallergens’ sensitization was investigated by using in vitro test Allergy screen, for 1461 patients diagnostics allergic at Mustapha Pasha Hospital in Algiers (Algeria), from the period between January 2016 and June 2019. Patients were categorized according to the demographic and clinical aspects. Statistical tests were applied to differentiate between age, gender, season of maximum attack and the polysensitization. The prevalence of sIgE was 55% (807/1461). The age groups of 16–40 years and ≤ 16 were more sensitized than that of ≥ 40 years. House dust mites, namely Dermatophagoides pteronyssinus and Dermatophagoides farinae, elicited most prevalent sIgE results (29.22% (427) and 25.05% (366), respectively), followed by Alternaria alternata and Cladosporium herbarum (17.72% (259) and 12.93% (189), respectively). Allergic rhinitis, urticaria, conjunctivitis and asthma were recorded as the common symptoms. Moreover, a significant correlation has been found in patients with polysensitization, especially between dust mites and molds. Following the increasing trend, house dust mite sensitization still held the dominance like in any other Mediterranean population reported earlier. Determining the allergic profile in this region will facilitate early diagnosis, management and prevention of allergic diseases.

Tnfaip3 expression in pulmonary conventional type 1 Langerin-expressing dendritic cells regulates T helper 2-mediated airway inflammation in mice.

BackgroundConventional type 1 dendritic cells (cDC1s) control anti‐viral and anti‐tumor immunity by inducing antigen‐specific cytotoxic CD8+ T‐cell responses. Controversy exists whether cDC1s also control CD4+ T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcription factor NF‐κB, might determine the precise outcome of Th‐cell differentiation upon encounter with cDC1s. To investigate the role of activated cDC1s in Th2‐driven immune responses, pulmonary cDC1s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF‐κB signaling.MethodsTo target pulmonary cDC1s, Cd207 (Langerin)‐mediated excision of A20/Tnfaip3 was used, generating Tnfaip3 fl/flxCd207 +/cre (Tnfaip3 Lg‐KO) mice. Mice were exposed to house dust mite (HDM) to provoke Th2‐mediated immune responses.ResultsMice harboring Tnfaip3‐deficient cDC1s did not develop Th2‐driven eosinophilic airway inflammation upon HDM exposure, but rather showed elevated numbers of IFNγ‐expressing CD8+ T cells. In addition, Tnfaip3 Lg‐KO mice harbored increased numbers of IL‐12–expressing cDC1s and elevated PD‐L1 expression in all pulmonary DC subsets. Blocking either IL‐12 or IFNγ in Tnfaip3 Lg‐KO mice restored Th2 responses, whereas administration of recombinant IFNγ during HDM sensitization in C57Bl/6 mice blocked Th2 development.ConclusionsThese findings indicate that the activation status of cDC1s, shown by their specific expression of co‐inhibitory molecules and cytokines, critically contributes to the development of Th2 cell–mediated disorders, most likely by influencing IFNγ production in CD8+ T cells.

Bcl6 and Blimp1 reciprocally regulate ST2+ Treg–cell development in the context of allergic airway inflammation

Bcl6 is required for the development of T follicular helper cells and T follicular regulatory (Tfr) cells that regulate germinal center responses. Bcl6 also affects the function of regulatory T (Treg) cells. The goal of this study was to define the functions of Bcl6 in Treg cells, including Tfr cells, in the context of allergic airway inflammation. We used a model of house dust mite sensitization to challenge wild-type, Bcl6fl/fl Foxp3-Cre, and Prdm1 (Blimp1)fl/fl Foxp3-Cre mice to study the reciprocal roles of Bcl6 and Blimp1 in allergic airway inflammation. In the house dust mite model, Tfr cells repress the production of IgE and Bcl6+ Treg cells suppress the generation of type 2 cytokine-producing cells in the lungs. In mice with Bcl6-deficient Treg cells, twice as many ST2+ (IL-33R+) Treg cells develop as are observed in wild-type mice. ST2+ Treg cells in the context of allergic airway inflammation are Blimp1 dependent, express type 2 cytokines, and share features of visceral adipose tissue Treg cells. Bcl6-deficient Treg cells are more susceptible, and Blimp1-deficient Treg cells are resistant, to acquiring the ST2+ Treg-cell phenotype invitro and invivo in response to IL-33. Bcl6-deficient ST2+ Treg cells, but not Bcl6-deficient ST2+ conventional T cells, strongly promote allergic airway inflammation when transferred into recipient mice. Lastly, ST2 is required for the exacerbated allergic airway inflammation in Bcl6fl/fl Foxp3-Cre mice. During allergic airway inflammation, Bcl6 and Blimp1 play dual roles in regulating Tfr-cell activity in the germinal center and in the development of ST2+ Treg cells that promote type 2 cytokine responses.

Oxidative stress is associated with atopic indices in relation to childhood rhinitis and asthma.

The association between oxidative stress and atopic diseases is uncertain. Several risk factors for atopic diseases have been identified, however, a comprehensive investigation of the relationship between oxidative stress markers and atopic indices related to atopic diseases is currently lacking. We investigated 132 children who completed a 7-years follow-up in a birth cohort. Oxidative stress markers including plasma glutathione peroxidase (GPx), myeloperoxidase (MPO), total anti-oxidant capacity (TAC), and urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured. Allergen-specific IgE levels, FeNO levels, and pulmonary function tests were also obtained. The activity of GPx and levels of MPO were inversely correlated to food (shrimp and crab) and house dust mite sensitization respectively. The 8-OHdG levels were strongly negatively correlated with FeNO levels (p<0.01). A significant positive correlation was found between TAC levels and pre-and post-bronchodilator FVC % and FEV1% predicted (p<0.05). All oxidative stress markers were not associated with the risk of atopic diseases. However, GPx-related crab sensitization and 8-OHdG related FeNO levels were significantly associated with increased risk of allergic rhinitis, while MPO-related mite sensitization and TAC-related pulmonary function parameters were strongly associated with risk of asthma (p<0.01). Oxidative stress is strongly correlated with allergic indices, potentially playing a role in the modulation of allergic responses contributing to atopic diseases.