Stimulation of naive ex vivo-isolated B cells with rFlaA:Betv1 results in a MyD88- and mTOR-dependent, but TLR5-independent differentiation of regulatory B cells. Regulatory B cells were shown to be CD19⁺CD24⁺CD1d⁺IgM⁺CD38⁺ and secreted both anti-inflammatory cytokine IL-10 and allergen-specific IgG antibodies. In co-cultures with TH2-biased Bet v 1-specific CD4⁺ T cells, rFlaA:Betv1-stimulated B cells suppressed Th2 responses.Abbreviations: BCR, B cell receptor; mDC, myeloid dendritic cell; MyD88, myeloid differentiation primary response 88; mTOR, mammalian target of rapamycin; rFlaA:Betv1, fusion protein of the TLR5-ligand flagellin A and the major birch pollen allergen Bet v 1; TLR5, Toll-like receptor 5.

Allergy-induced protection against GBM is recapitulated in a preclinical syngeneic mouse model. Allergic airway inflammation skews microglia toward pro-inflammatory and antigen-presenting like-states, uncovering a gene-signature in mice associated with improved patient survival and reduced local immunosuppression in glioma patients. Allergic airway inflammation promotes the recruitment of CD4⁺T-cells within the tumor microenvironment and mitigates glioma-induced systemic immunosuppression.Abbreviations: AAI, allergic airway inflammation; GBM, glioblastoma; Neu, neutrophil; TME, tumor-microenvironment.

Initiation of allergen-specific Th2 cell responses generates an IL-2-mediated activation of Tregs. IL-2-activated T cells exert an immunosuppressive effect on effector T cells. In vivo exposure to peanut induces a delayed and persistent activation of Tregs.Abbreviations: ICOS, inducible T-cell co-stimulator; IL, interleukin; LAP, latency-associated peptide; OX40, TNF receptor superfamily member 4; PD1, programmed cell death protein 1; Th, T helper cell; Treg, regulatory T cell.

Deficiency of EP2 rather than EP4 enhances IL-33-induced lung ILC2 responses and eosinophilic inflammation. Both EP2 and EP4 agonism represses IL-33-induced mouse lung ILC2 responses. PGE₂-EP2/EP4-cAMP signaling inhibits ILC2 survival, proliferation and effector function through disturbing the IL-2/IL-7/IL-33-activated metabolic program in ILC2s.Abbreviations: AMP, adenosine monophosphate; cAMP, cyclic adenosine monophosphate; EP2, E prostanoid receptor 2; EP4, E prostanoid receptor 4; ILC2, group 2 innate lymphoid cell; NF-κB, nuclear factor kappa B; PDE, phosphodiesterase; PGE₂, prostaglandin E₂; STAT5: signal transducer and activator of transcription 5.

Individual HDM sensitization patterns to nine HDM allergens were investigated in 384 patients with different allergic diseases. Sensitization to more than three HDM allergens was associated with the simultaneous occurrence of multiple allergic diseases. Der p 5 and Der p 21 were associated with allergic asthma and atopic dermatitis. High Der p 20-IgE was strongly associated with severe atopic dermatitis.Abbreviations: AA, allergic asthma, AD, atopic dermatitis, AR, allergic rhinitis, HDM, house dust mite.

In birch-dominated areas, Bet v 1 is considered as primary sensitizer of IgE-mediated allergies to pollen from birch-related trees. T-cell lines established with Bet v 1-homologous pollen allergens show limited cross-reactivity with Bet v 1. Despite high amino acid sequence homology of major Fagales allergens with Bet v 1 T-cell cross-reactivity is restricted to very few epitopes of the major birch pollen allergen. Two dominant T-cell epitopes of Aln g 1 indicate genuine sensitizing capacity.Abbreviation: TCL, T cell line.

We identified a novel population of IgG⁺IL4R⁺CD23⁺ type 2-marked memory B cells that are increased in peripheral blood of subjects with asthma or atopic dermatitis compared to non-atopic subjects. Type 2-marked IgG memory B cell frequency correlates with circulating levels of IgE antibodies. They express IL-4/IL-13 regulated genes, ie FCER2/CD23, IL4R, IL13RA1, and IGHE. B cells from atopic subjects generate more IgE cells when stimulated in ex vivo cultures than B cells from non-atopic subjects. IgG⁺IL4R⁺CD23⁺ have the highest ability to switch to IgE among IgG memory B cells.Abbreviations: BAFF, B cell activating factor; CD40L, CD40 ligand; FCER2, Fc epsilon receptor II; Ig, immunoglobulin; IGH, immunoglobulin heavy constant; IL, interleukin; IL4RA, IL-4 receptor subunit alpha; IL13RA1, IL-13 receptor subunit alpha 1; IU/ml, international units per milliliter; scRNAseq, single cell RNA sequencing

Th2 cells were higher in women with severe vs mild/moderate asthma and men of either phenotype; Th2 cell numbers correlated with ICS in women, but not men. ERα antagonized GC-mediated Th2 cell death, increased CRTh2 and reversed GC inhibition of Th2 cytokines induced by PGD₂. ERα activation may drive asthma severity in women by interfering with GC.Abbreviations: Th2, T helper 2 cells; ICS, total daily dose of inhaled corticosteroid; GC, glucocorticosteroid; ERα, estrogen receptor alpha; PGD₂, prostaglandin D₂; CRTh2, chemoattractant receptor-homologous expressed on Th2 cells.

Non-obese versus obese women with asthma underwent methacholine provocation coupled with CT scanning to determine MLD_e/i per step. Mixed models on standardized response curves determined an obesity x dose interaction for MLD_e/i. Greater MLD_e/i slopes for obese patients were pinpointed in the first two-thirds of curves, corresponding to higher bronchial responsiveness during methacholine provocation.Abbreviations: CT, computed tomography; FEV ₁, forced expiratory volume in 1 second (% predicted); FVC, forced vital capacity (% predicted); MLD_e/i, expiratory: inspiratory ratios of mean lung density; PD20, the end of methacholine provocation, when a drop of at least 20% in FEV1 is observed

This study examines whether selected skin biomarkers in stratum corneum tape strips from infants with clinically normal skin at 2 months of age are different in children who develop AD in the first year of life. Skin CCL17/TARC levels as well as lipid markers, including [P], [DS] and CER [DS] show significant alteration between children who developed AD and those who did not. ROC curve demonstrate that phytosphingosine, and to a lesser extend CCL17/TARC separate children who developed AD from those who did not.Abbreviations: AD, atopic dermatitis; CCL17/TARC, C-C motif chemokine ligand 17/ TARC, thymus- and activation-regulated chemokine; CER [DS], ceramide class with dihydrosphingosine as a sphingoid base; [DHS], dihydrosphingosine (sphinganine) [PS], phytosphingosine.

This study retrospectively examines the treatment course and outcome of adult patients that completed OIT and compares it with OIT in children and adolescents. Significantly more adults undergoing milk OIT failed treatment compared with children and adolescents, while failure rates in adults undergoing non-milk OIT is low and comparable with children and adolescents. Adults experienced more adverse reactions requiring epinephrine injection, both during in-clinic up-dosing and during home treatment, especially in milk OIT. In non-milk OIT, the safety profile for home reactions was comparable with children and adolescents.Abbreviation: OIT, oral immunotherapy.

This post hoc analysis assessed surgery-specific endpoints from the SYNAPSE trial of mepolizumab in patients with severe CRSwNP. Mepolizumab versus placebo reduced the risk of undergoing sinus surgery irrespective of the patient characteristics assessed. Mepolizumab reduces the need for repeat sinus surgery in patients with severe CRSwNP.Abbreviations: CI, confidence interval; CRSwNP, chronic rhinosinusitis with nasal polyps; HR, hazard ratio, SoC standard of care.

Using recombinant Lol p 1 tetramers, allergen-specific B_mem from patients allergic to ryegrass pollen were examined before and after 4 months of SLIT. Single-cell RNA sequencing revealed that SLIT drives two unique transcriptional B_mem fates, typified by CD23, IgG4, IgE, CD29, and IL13Ra1 expression. Flow cytometry confirmation revealed that CD29 expression is the best positive predictor of SLIT effects.Abbreviations: AR, allergic rhinitis; B_mem, memory B cells; FCER2, Fc epsilon receptor II; IGH, immunoglobulin heavy chain; IL13RA1, interleukin 13 receptor subunit alpha 1; ITGB1, integrin subunit beta 1; SLIT, sublingual immunotherapy.

We identified seven allergic disease trajectories up to adolescence, which are corresponding to clinical observation in the German GINIplus and LISA studies and replicated the results in the Swedish BAMSE cohort. The clusters can be characterized using polygenic risk scores and early-life determinants, which support the hygiene hypothesis. The clusters also pose clinical implications for allergic sensitization, increasing with number of present allergic diseases, and lung function.Abbreviations: BAMSE, Barn/Child Allergy Milieu Stockholm Epidemiology; GINIplus, German Infant Study on the Influence of Nutrition Intervention plus Air pollution and Genetics on Allergy Development; LISA, Influence of Life-style factors on Development of the Immune System and Allergies in East and West Germany study; PRS, polygenic risk score.