Mite Extract Research Articles

MrgprA3+ Primary Sensory Neurons Mediate Acute Allergic Itch Responses in Atopic Dermatitis Model Mice.

Itch is a prominent symptom of atopic dermatitis (AD). However, the underlying mechanism remains complex and has not yet been fully elucidated. Mas-related G protein-coupled receptor A3 (MrgprA3) has emerged attention as a marker of primary sensory neurons that specifically transmit itch signals; however, its involvement in AD-related itch has not been extensively explored. In this study, we developed an AD itch mouse model by repeatedly applying house dust mite (HDM) extract to barrier-impaired skin via a special diet. To clarify the role of MrgprA3+ neurons in itch behavior in our AD model, we adopted a toxin receptor-mediated cell knockout strategy using transgenic mice in which the diphtheria toxin receptor (DTR) gene was placed under the control of the Mrgpra3 promoter. When the HDM extract was repeatedly applied to the face and back skin of special diet-fed mice, the mice exhibited AD-like dry and eczematous skin lesions accompanied by three types of itch-related behaviors:1) spontaneous scratching, 2) acute scratching after antigen challenge, and 3) light touch-evoked scratching. Upon diphtheria toxin administration, substantial depletion of DTR+/MrgprA3+ neurons was observed in the dorsal root ganglion. Ablation of MrgprA3+ neurons suppressed acute itch responses after HDM application, whereas spontaneous and touch-evoked itch behaviors remained unaffected. Our findings unequivocally demonstrate that in our AD model, MrgprA3+ primary sensory neurons mediate acute allergic itch responses, whereas these neurons are not involved in spontaneous itch or alloknesis.

Expression reduction and a variant of a P450 gene mediate chlorpyrifos resistance in Tetranychus urticae Koch

IntroductionUnderstanding how insects and mites develop resistance to chlorpyrifos is crucial for effective field management. Although extensive research has demonstrated that T. urticae exhibits high resistance to chlorpyrifos, the specific resistance mechanism remains elusive. Investigating this mechanism could provide valuable insights for pest control strategies. ObjectivesThis study aimed to reveal the mechanism of chlorpyrifos resistance in T. urticae. MethodsThe expression level of the CYP392D8 gene in T. urticae strains were analyzed using real- time quantitative PCR and western blot techniques. Functional validation of CYP392D8 was conducted through RNAi and heterogeneous expression. The production of chlorpyrifos-oxon in both resistant and susceptible strains were quantified using LC-MS/MS. Furthermore, the metabolic capabilities of CYP392D8 variants were verified using HPLC-MS and molecular docking. ResultsThe results showed the expression of CYP392D8 was reduced in some Chinese resistant populations and mites with knocked down CYP392D8 showed decreased susceptibility to chlorpyrifos. Chlorpyrifos-oxon, the active metabolite of chlorpyrifos, was generated when chlorpyrifos was incubated with recombinant CYP392D8 protein in vitro. And a higher efficiency of chlorpyrifos-oxon formation was observed with the CYP392D8-S variant from susceptible mites compared to the CYP392D8-R variant from resistant mites. After treatment with low doses of chlorpyrifos, susceptible mite extracts produced substantial amounts of chlorpyrifos-oxon, while resistant mites only showed trace amounts. In addition, molecular docking studies showed that CYP392D8-S had a higher binding capacity to chlorpyrifos than the CYP392D8-R variant. ConclusionThis study reveals a mechanism of insecticide resistance due to the bioactivation reduction in combination with the sequence variation in a pest mite. These findings provide an important theoretical bias for management strategies of mites in the field and comprehensive control.

Endogenous LXR signaling controls pulmonary surfactant homeostasis and prevents lung inflammation

Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRβ, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRβ as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases.Graphical

Efficacy and safety of subcutaneous immunotherapy with polymerized allergen mixtures in polyallergic patients – ARES observational study

ABSTRACT Background Administration of allergen mixtures of many components comprises the most common approach for American allergists regarding the management of polyallergic patients. European allergists, however, are more reluctant to this type of treatment due to the potential drawbacks of mixing extracts. Research design and methods To assess the efficacy and safety of subcutaneous immunotherapy (SCIT) with polymerized allergen mixtures without dilutional effect in polyallergic patients. This observational, prospective, multicenter study included patients (between 5 and 60 years) with respiratory allergic diseases that had been prescribed with SCIT with mixtures of two pollen or mite extracts. Changes in Symptoms and Medication Score (SMS) and in rhinitis quality of life questionnaire (RQLQ), subjective clinical improvement, treatment satisfaction and tolerability were assessed after the 1-year treatment. Results A total of 115 patients were included in the assessment. Mean global SMS decreased from 3.5 (SD = 1.1) to 1.6 (SD = 1.2) points, with a mean absolute reduction of 1.6 (SD = 1.3) points in the RQLQ score (p < 0.001, Wilcoxon test). General subjective clinical improvements and a good treatment satisfaction and tolerability were observed. Conclusion SCIT with polymerized allergen mixtures from either pollen or mite extracts proved to be an effective and safe treatment option for polyallergic patients suffering from allergic respiratory diseases.

Enhancing quality of life with 3-year course of sublingual immunotherapy for house dust mite-induced allergic rhinitis: An observational prospective study in real-life settings

PurposeThis prospective study aims to provide further supportive evidence by assessing the sustained effectiveness and safety of sublingual immunotherapy (SLIT) using a vaccine containing house dust mite (HDM) extracts in patients diagnosed with allergic rhinitis (AR) with/without conjunctivitis (AR/C). Materials and methodsAR/C patients (n = 111, SLIT group: 57, control group: 54) allergic to HDM were treated with standardized SLIT drops or symptomatic drugs from October to December in 2020. The patients were directed by the investigators to attend annual hospital visits for the assessment of various parameters including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), visual analog scale (VAS), total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total medication score (TMS). During the study period, all participants were mandated to maintain comprehensive records of any adverse events (AEs) on diary cards, which were then communicated to the investigators via telephone. ResultsAt baseline (2020), TNSS, TOSS, TMS, VAS, and RQLQ scores were comparable between SLIT and control groups (P > 0.05). After one year of treatment (2021), significant reduction in all scores compared to the baseline for both groups (P < 0.001). At the end of the second year of treatment (2022), TNSS and RQLQ score in the SLIT group continued to decrease significantly compared to 2021 (P < 0.05). In the third year (2023), the control group showed a rebound in TNSS, TOSS, TMS, and RQLQ scores, significant differences compared to 2022 or 2021 (P < 0.05). Besides, the SLIT group had significantly lower scores across all domains of RQLQ compared to the control group (P < 0.001). Symptomatic treatment influenced the scores of Nasal Symptoms, Eye Symptoms, Practical Problems, and Emotions domains significantly in 2023 compared to 2021 or 2022 (P < 0.05). Within the SLIT group, no significant differences in TNSS, TMS, VAS, and RQLQ scores were observed between monosensitized and polysensitized patients throughout the three years of treatment (P > 0.05). All AEs were mild to moderate. ConclusionThe 3-year course of HDM-SLIT has shown significant therapeutic efficacy and a favorable safety profile in patients with AR/C. Importantly, our study presents initial evidence suggesting that the greater impact of AR/C on quality of life (QoL) may primarily stem from nasal symptoms, eye symptoms, practical issues, and emotional well-being.

Obesity Enhances Non-Th2 Airway Inflammation in a Murine Model of Allergic Asthma.

Obese patients with asthma present with aggravated symptoms that are also harder to treat. Here, we used a mouse model of allergic asthma sensitised and challenged to house dust mite (HDM) extracts to determine whether high-fat-diet consumption would exacerbate the key features of allergic airway inflammation. C57BL/6 mice were intranasally sensitised and challenged with HDM extracts over a duration of 3 weeks. The impact of high-fat-diet (HFD) vs. normal diet (ND) chow was studied on HDM-induced lung inflammation and inflammatory cell infiltration as well as cytokine production. HFD-fed mice had greater inflammatory cell infiltration around airways and blood vessels, and an overall more severe degree of inflammation than in the ND-fed mice (semiquantitative blinded evaluation). Quantitative assessment of HDM-associated Th2 responses (numbers of lung CD4+ T cells, eosinophils, serum levels of allergen-specific IgE as well as the expression of Th2 cytokines (Il5 and Il13)) did not show significant changes between the HFD and ND groups. Interestingly, the HFD group exhibited a more pronounced neutrophilic infiltration within their lung tissues and an increase in non-Th2 cytokines (Il17, Tnfa, Tgf-b, Il-1b). These findings provide additional evidence that obesity triggered by a high-fat-diet regimen may exacerbate asthma by involving non-Th2 and neutrophilic pathways.

Increased CD123 + HLA-DR- Granulocytes in Allergic Rhinitis and Influence of Allergens on Expression of Cell Membrane Markers.

It is reported that CD123 + HLA-DR- cells in PBMC are basophils, and CD203c, CD63, and FcεRI molecules are activation markers of basophils. However, little is known of CD123 + HLA-DR-cells in blood granulocytes. To investigate the presence of CD123 + HLA-DR- cells in the blood granulocytes and peripheral PBMC of patients with allergic rhinitis (AR), as well as the impact of allergens on the cell membrane markers of basophils. Flow cytometry was used to detect the expression of the membrane molecules. While CD123 + HLA-DR- PBMCs are representative of basophils, their presence did not significantly change in patients with AR. In contrast, both the percentage and number of CD123 + HLA-DR- granulocytes, which make up only up to 50% of basophils, were significantly increased in patients with seasonal (sAR) and perennial AR (pAR). CD63+, CD203c+, and FcεRIα+ cells within CD123 + HLA-DR- granulocytes also showed enhanced activity in patients with AR. Allergen extracts from house dust mite allergen extract (HDME) and Artemisia sieversiana wild extract further increased the number of CD123 + HLA-DR- cells in granulocytes of sAR and pAR patients, as well as in PBMCs of pAR patients. The use of CD123 + HLA-DR- granulocytes and PBMC may not be sufficient for diagnosing AR. Allergens could potentially contribute to the development of AR by influencing the number of CD123 + HLA-DR- cells, as well as the expression of CD63, CD203c, and FcεRIαin these cells.

Fiber rich food suppressed airway inflammation, GATA3 + Th2 cells, and FcεRIα+ eosinophils in asthma.

Allergic Asthma is a disease presenting various endotypes and no current therapies act curative but alleviate disease symptoms. Dietary interventions are gaining increasing importance in regulating immune responses. Furthermore, short chain fatty acids (SFCA), as the main products of dietary fiber's fermentation by the gut bacteria, ameliorate the pathogenesis and disease burden of different illnesses including asthma. Nevertheless, the connection and crosstalk between the gut and lung is poorly understood. In this work, the role of high fiber diet on the development of allergic asthma at baseline and after exacerbation of disease induced by respiratory viruses was investigated. Hereby, SCFA in serum of asthmatic and non-asthmatic pre-school children before and after airway disease symptoms were analyzed. Moreover, the effect of high fiber diet in vivo in a murine model of house dust mite extract (HDM) induced allergic asthma and in the end in isolated lung and spleen cells infected ex vivo with Rhinovirus was analyzed. In this study, a decrease of the SCFA 3-Hydroxybutyric acid in serum of asthmatic children after symptomatic episodes at convalescent visit as compared to asthmatic and control children at baseline visit was observed. In experimental asthma, in mice fed with high fiber diet, a reduced lung GATA3 + Th2 type mediated inflammation, mucus production and collagen deposition and expression of Fc epsilon receptor Ia (FcεRIa) in eosinophils was observed. By contrast, the CD8+ memory effector T cells were induced in the lungs of asthmatic mice fed with high fiber diet. Then, total lung cells from these asthmatic mice fed with either standard food or with fiber rich food were infected with RV ex vivo. Here, RV1b mRNA was found significantly reduced in the lung cells derived from fiber rich food fed mice as compared to those derived from standard food fed asthmatic mice. Looking for the mechanism, an increase in CD8+ T cells in RV infected spleen cells derived from fiber rich fed asthmatic mice, was observed. Convalescent preschool asthmatic children after a symptomatic episode have less serum ß-Hydroxybutyric acid as compared to control and asthmatic children at baseline visit. Fiber rich diet associated with anti-inflammatory effects as well as anti-allergic effects by decreasing Type 2 and IgE mediated immune responses and inducing CD8+ memory effector T cells in a murine model of allergic asthma. Finally, ex vivo infection with Rhinovirus (RV) of total lung cells from asthmatic mice fed with fiber rich food led to a decreased RV load as compared to mice fed with standard food. Moreover, spleen cells derived from asthmatic mice fed with fiber rich food induced CD8+ T cells after ex vivo infection with RV. Dietary interventions with increased content in natural fibers like pectins would ameliorate asthma exacerbations. Moreover, respiratory infection in asthma downregulated SCFA in the gut contributing to asthma exacerbations.

DerP1, a house dust mite protease, directly activates airway vagal afferents and induces airway hyperreactivity after chronic exposure

Airway hyperreactivity (AHR) is one of the main symptoms of allergic asthma. Current therapeutics used in the treatment of allergic asthma do not target the AHR. Airway sensory afferents have been shown to be critical in AHR, but the mechanisms remain elusive. We have previously shown that house dust mite (HDM) extract, which contains multiple different proteases, can directly activate these airway sensory afferents in the lung via PAR1 receptors. In this study we identified the most potent protease DerP1 is capable of directly and robustly activating airway sensory vagal afferents. DerP1 caused a significant release of CGRP, a neuropeptide released after nerve terminal activation, from the airways. We observed that DerP1 caused a calcium influx in 65% of TRPV1 positive lung specific neurons. We also observed that in our two-photon ex vivo imaging of the vagal ganglia of PirtCre;R26 ‐ GCaMP6s mice, DerP1 caused a robust activation of approximately 60% of naïve airway-specific C-fibers. Calcium imaging of the lung specific vagal neurons from wild type, TRPA1 KO and TRPV1 KO revealed that the DerP1 mediated activation was absent in TRPV1 KO mice neurons. We then found that mice exposed to DerP1 chronically over a period of 12 days (without an adjuvant) had significant AHR and Th2 mediated airway inflammation. Our data suggests that direct activation of airway vagal C-fiber afferents by DerP1 via TRPV1 chronically leads to airway hyperreactivity and Th2 mediated airway inflammation. Warren Alpert Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Utility of silver birch and house dust mite extracts derived from licensed sublingual tablets for nasal allergen challenge.

Nasal allergen challenge (NAC) is used to investigate the effects of allergen exposure and assess treatment efficacy in allergic rhinitis (AR). This study aims to establish dose-responses to NAC using licensed silver birch (SB) pollen and house dust mite (HDM) sublingual tablets as sources of the allergen extracts in participants with AR. Sixteen volunteers with HDM-induced perennial AR and 15 volunteers with SB pollen-induced seasonal rhinitis underwent a graded up-dosing NAC with extracts derived from HDM allergen (Acarizax®) and SB (Itulazax®) tablets, respectively. Total nasal symptom score (TNSS, range 0-12) and peak nasal inspiratory flow (PNIF) were recorded before, at 10min and at the end of the NAC. The dose of each allergen that provoked a TNSS of at least 7 ("provoking dose 7") in most allergic participants was identified. NACs using the "provoking dose 7" were performed on 5 non-allergic individuals to test for irritant effects. The "provoking dose 7" of HDM extract was used in a subgroup of two SB allergic, non-HDM allergic, volunteers, and vice versa for SB extract, to test for allergen specificity of the responses. Most patients experienced a TNSS of at least 7/12 at a median concentration of 1500AU/mL for both SB pollen and HDM. The average decline in PNIF at this dose was 63.15% for SB and 63.99% for HDM. NACs using the 1500AU/mL concentrations were performed on 5 non-allergic individuals with no symptomatic or PNIF response. 1500AU/mL of HDM extract produced no symptoms in SB allergics nor 1500AU/mL SB extract in HDM allergics. For both SB and HDM extracts, the optimal allergen dose for NAC to cause a moderate-severity response ("provoking dose 7/12") was 1500AU/mL. Licensed sublingual allergen tablets provide a readily available and inexpensive source of SB and HDM extracts for use in future interventional studies in AR.

Safety of subcutaneous immunotherapy with Novo-Helisen-Depot in the children: a retrospective analysis from a single center in Northern China.

Little is known about the safety of mite extract product Novo-Helisen Depot (NHD) as subcutaneous immunotherapy (SCIT) in the children with mite allergy especially immediate/late local reaction (LRs). We conducted a retrospective study analyzing the adverse events of the children undergoing subcutaneous immunotherapy with NHD. Adverse events included local and systemic adverse reactions (SRs) at the very early and late stage. The correlation of the basic characteristics, laboratory analysis results, LRs and SRs were analyzed. Two hundred and eighty-seven patients received at least 15 months of subcutaneous immunotherapy with NHD were included in the analysis. Skin-prick testing (SPT) results of D. pteronyssinus was associated with an increased risk of immediate LRs in build-up phase (OR = 1.53, 95% CI: 1.02, 2.37) and delayed LRs in maintenance phase (OR = 1.58, 95% CI: 1.05, 2.46), while SPT results of D. farinae was associated with an increased risk of SRs (OR = 3.22, 95% CI: 1.17, 10.00) and severe SRs (OR = 7.68, 95% CI: 1.13, 109.50). Serum IgE level of D. pteronyssinus was associated with an increased risk of SRs (OR = 1.01, 95% CI: 1.00, 1.03). Patients with both asthma and allergic rhinitis was associated with an increased risk of SR, and severe SRs (P < 0.05). NHD as SCIT is safe. The children with higher SPT level with D. farinae or D. pteronyssinus, higher serum IgE level of D. pteronyssinus, children with both asthma and allergic rhinitis, and the children with treatment interruption had higher risk of adverse events.

Frequency of sensitization to shrimp with house dust mite immunotherapy with polymerized extracts

To evaluate the risk of IgE sensitization and symptoms to shrimp in a population that has received AIT with polymerized mite extract. Patients with allergic rhinitis sensitized to dust mites (Dermatophogides spp) with an indication for mite AIT were included. Those patients who had not yet received AIT or had received less than 6 doses were included as controls and those who had received more than 24 doses of AIT were included as cases. Sensitization to shrimp was assessed by skin prick test with complete shrimp extract and/or shrimp-specific IgE. A total of 68 patients were included; 47 cases and 21 controls. When calculating the odds ratio of sensitization according to time with immunotherapy we observed that there were no differences between the group of cases and controls (OR 0.76 95% CI 0.26 to 2.22 p 0.7 by MacNemar technique). Factors such as consumption or not of shrimp and frequency of consumption do not seem to be related to the outcome. In contrast to what was reported with aqueous extracts, we observed that AIT with polymerized extracts is not a risk factor for shrimp sensitization. It is necessary to reproduce these results with a larger sample size to explore other factors.

The impact of IL-10 and IL-17 on myeloid-derived suppressor cells in vitro and in vivo in a murine model of asthma.

Myeloid-derived suppressor cells (MDSCs) hold promise for clinical applications due to their immunosuppressive properties, particularly in the context of inflammation. In the present study, the number and immunosuppressive activity of MDSCs isolated from naïve Il10-/-, Il17-/-, and WT mice as control, as well as from house dust mite extract (HDM)-induced asthmatic Il10-/- and Il17-/- mice, were investigated. IL-10 deficiency increased the number of polymorphonuclear (PMN)-MDSCs in the lung, spleen, and bone marrow, without concurrent impairment of their suppressive activity in vitro. In the asthma model, the IL-17 knockout was concomitant with a lower number and activity of monocytic (M)-MDSCs and an altered inflammatory reaction with impaired lung function. Additionally, we found a higher baseline inflammation of the Il17-/- mice in the lung, manifested in increased airway resistance. We conclude that the impact of IL-10 and IL-17 deficiency on MDSCs differs in the context of inflammation. Accordingly, the in vitro experiments demonstrated an increased number of PMN-MDSCs across tissues in Il10-/- mice, which indicates that IL-10 might serve a pivotal role in preserving immune homeostasis under physiological circumstances. In the context of HDM-induced airway inflammation, IL-17 was found to be an important player in the suppression of pulmonary inflammation and regulation of M-MDSCs.

Early-life house dust mite aeroallergen exposure augments cigarette smoke-induced myeloid inflammation and emphysema in mice

BackgroundLongitudinal studies have identified childhood asthma as a risk factor for obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) where persistent airflow limitation can develop more aggressively. However, a causal link between childhood asthma and COPD/ACO remains to be established. Our study aimed to model the natural history of childhood asthma and COPD and to investigate the cellular/molecular mechanisms that drive disease progression.MethodsAllergic airways disease was established in three-week-old young C57BL/6 mice using house dust mite (HDM) extract. Mice were subsequently exposed to cigarette smoke (CS) and HDM for 8 weeks. Airspace enlargement (emphysema) was measured by the mean linear intercept method. Flow cytometry was utilised to phenotype lung immune cells. Bulk RNA-sequencing was performed on lung tissue. Volatile organic compounds (VOCs) in bronchoalveolar lavage-fluid were analysed to screen for disease-specific biomarkers.ResultsChronic CS exposure induced emphysema that was significantly augmented by HDM challenge. Increased emphysematous changes were associated with more abundant immune cell lung infiltration consisting of neutrophils, interstitial macrophages, eosinophils and lymphocytes. Transcriptomic analyses identified a gene signature where disease-specific changes induced by HDM or CS alone were conserved in the HDM-CS group, and further revealed an enrichment of Mmp12, Il33 and Il13, and gene expression consistent with greater expansion of alternatively activated macrophages. VOC analysis also identified four compounds increased by CS exposure that were paradoxically reduced in the HDM-CS group.ConclusionsEarly-life allergic airways disease worsened emphysematous lung pathology in CS-exposed mice and markedly alters the lung transcriptome.

Intermittent hypoxic pretreatment exacerbates house dust mite-induced asthma airway inflammation.

Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF-κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. Compared to the RA and IH groups, HDM-treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF-κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). IHP treatment potentially exacerbates HDM-induced airway inflammation in asthma, with the involvement of NF-κB, particularly under high-dose allergen stimulation.

The safety and tolerability of a one strength dose-escalation scheme for subcutaneous immunotherapy with a native house dust mite extract in Chinese children: A multicenter, randomized, open label clinical trial

BackgroundAllergen immunotherapy (AIT) is still the only treatment that may affect the natural cause of allergic disease. This study is to investigate whether an accelerated up-dosing scheme for subcutaneous allergen immunotherapy (SCIT) using a native house dust mite (HDM) allergen extract is as safe as the standard 3-strengths dose-escalation scheme in children with moderate to severe allergic rhinitis or rhinoconjunctivitis with or without asthma in China. MethodsIn this multicenter, open label, randomized controlled trial, the children aged 5–14 years were randomized 1:1 either to One Strength group or the Standard group. The dose escalation scheme for patients in the One Strength group included 6 injections of strength 3, whereas the Standard group comprised 14 injections using strength 1, 2, and 3. All treatment-emergent adverse events (TEAEs) were recorded and analyzed. The 5-point Likert scale was used to assess tolerability (ChiCTR2100050311). ResultsOverall, 101 children were included in the Safety Set (One Strength group: 50 vs. Standard group: 51). A total of 26 TEAEs were reported for 15 children. TEAEs related to AIT occurred in 10 % of the children in the One Strength group and 11.8 % of the Standard group. The number of systemic adverse reactions was comparable in both groups (One Strength: 5 vs. Standard: 4). No serious TEAEs was recorded for either group. 90.0 % of patients in the One Strength group reached the maintenance dose without an interventional dose adjustment due to adverse events, compared to 78.4 % in the Standard group. All patients who completed the dose-escalation phase reached the recommended maintenance dose of 1.0 ml of strength 3.Investigators and patients rated the tolerability of the One Strength regimen slightly better than the Standard scheme. ConclusionsThis exploratory study suggests that the accelerated One Strength dose-escalation scheme is comparable in safety and tolerability to the Standard regimen. However, due to the preliminary nature and small sample size, further research with larger sample sizes and robust study designs is necessary for confirmation.

Direct exposure to CpG and specific antigens mitigate airway allergy through modulating dendritic cell properties

BackgroundCpG oligodeoxynucleotide (CpG-ODN; CpG, in short) has been employed as an adjuvant in allergen specific immunotherapy (AIT) to treat allergic diseases. The underlying mechanism needs to be further explained. The aim of this study is to examine the mechanism by which CpG and dust mite extracts (DME, a specific antigen) alleviate experimental airway allergy. MethodsDME was used as the specific allergen to establish an airway allergy mouse model. The mice were directly exposed to DME and CpG through nasal instillations (the CpG.DME therapy). The response of DCs and allergic responses in the airways were assessed using immunological approaches. ResultsThe airway allergy reaction was effectively suppressed by CpG.DME therapy. The administration of CpG or DME alone did not have any significant suppressive effects on the airway allergic response. Direct exposure to CpG.DME induced type 1 DCs (DC1s) and plasmacytoid DCs (pDCs), while CpG alone induced DC1s and DME alone induced DC2s in the airway tissues. Both DC1s and pDCs were required for the induction of type 1 regulatory T cells in the airway tissues by CpG.DME therapy. Depletion of either pDCs or DC1s abolished the induction of Tr1 cells, and abolished the suppressive effects on airway allergic response by the CpG.DME therapy. ConclusionsDirect exposure to CpG.DME induces DC1s and pDCs in the airway tissues. DC1s in synergy with pDCs induce type 1 regulatory T cells. The CpG.DME therapy is effective in suppressing allergic responses in mice with airway allergy.

Effectiveness of allergen immunotherapy with house dust mite extract for pediatric bronchial asthma.

Aim: We compared the effectiveness of rush subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) using standardized house dust mite (HDM) extract for pediatric bronchial asthma (BA). Methods: We followed the pediatric BA treatment score during 3 years of treatment. We assessed the median time to no longer requiring long-term control pharmacotherapy (LTCP) for BA (LTCP-free). We compared the outcomes after adjustment for confounding factors and propensity score matching. Results: Patients in the HDM SCIT group achieved the LTCP-free status significantly earlier than those in the HDM SLIT group after adjustment for confounding factors and propensity score matching. Conclusion: Patients treated for pediatric BA with rush HDM SCIT had earlier onset of therapeutic effects than those with HDM SLIT.

IL-6 mediates olfactory dysfunction in a mouse model of allergic rhinitis

BackgroundImmune-inflammatory response is a key element in the occurrence and development of olfactory dysfunction (OD) in patients with allergic rhinitis (AR). As one of the core factors in immune-inflammatory responses, interleukin (IL)-6 is closely related to the pathogenesis of allergic diseases. It may also play an important role in OD induced by diseases, such as Sjögren’s syndrome and coronavirus disease 2019. However, there is no study has reported its role in OD in AR. Thus, this study aimed to investigate the role of IL-6 in AR-related OD, in an attempt to discover a new target for the prevention and treatment of OD in patients with AR. MethodsDifferential expression analysis was performed using the public datasets GSE52804 and GSE140454 for AR, and differentially expressed genes (DEGs) were obtained by obtaining the intersection points between these two datasets. IL-6, a common differential factor, was obtained by intersecting the DEGs with the General Olfactory Sensitivity Database (GOSdb) again. A model of AR mice with OD was developed by sensitizing with ovalbumin (OVA) to verify the reliability of IL-6 as a key factor of OD in AR and explore the potential mechanisms. Furthermore, a supernatant and microglia co-culture model of nasal mucosa epithelial cells stimulated by the allergen house dust mite extract Derp1 was established to identify the cellular and molecular mechanisms of IL-6-mediated OD in AR. ResultsThe level of IL-6 in the nasal mucosa and olfactory bulb of AR mice with OD significantly increased and showed a positive correlation with the expression of olfactory bulb microglia marker Iba-1 and the severity of OD. In-vitro experiments showed that the level of IL-6 significantly increased in the supernatant after the nasal mucosa epithelial cells were stimulated by Derp1, along with significantly decreased barrier function of the nasal mucosa. The expression levels of neuroinflammatory markers IL-1β and INOS increased after a conditioned culture of microglia with the supernatant including IL-6. Then knockdown (KD) of IL-6R by small interfering RNA (siRNA), the expression of IL-1β and INOS significantly diminished. ConclusionIL-6 plays a key role in the occurrence and development of OD in AR, which may be related to its effect on olfactory bulb microglia-mediated neuroinflammation.

Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma.

Allergic asthma generally starts during early life and is linked to substantial tissue remodeling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLSs), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas. Central to the blood vessel structure, the loss of pericyte coverage was driven by mast cell (MC) proteases, such as tryptase, that can induce pericyte retraction and loss of the critical adhesion molecule N-cadherin. Furthermore, spatial transcriptomics of pediatric asthmatic endobronchial biopsies suggests intense vascular stress and remodeling linked with increased expression of MC activation pathways in regions enriched in blood vessels. These data provide previously unappreciated insights into the pathophysiology of allergic asthma with potential long-term vascular defects.