Allergy & Immunology

Environmental immune imprinting dampens type 2 allergic responses in mice

In a murine allergy model, exposure to immunostimulatory environments generated cross-reactive adaptive immune memory that suppressed type 2 responses to allergens. Prior environmental exposure impeded new allergic sensitization and reduced established allergic manifestations upon subsequent allergen challenge. Cross-reactive protection arose even when protein sequence similarity between environmental antigens and allergens was low. Tolerogenic cross-reactivity thus provides a mechanistic link between diverse microbial environments and reduced IgE‑mediated allergy risk. 1

Airway neutrophilic inflammation tracks with conserved microbiota patterns in global youth asthma

In 488 young participants from five countries, airway microbiota and inflammatory phenotypes varied substantially by geography and asthma status. Ugandan participants showed higher sputum neutrophils, greater microbial diversity, and higher total bacterial loads than other sites. Across centers, higher airway neutrophil proportions correlated with distinct microbiota dissimilarity and increased bacterial abundance, including H. influenzae and M. catarrhalis. Eosinophil proportions were less strongly linked to microbiota structure and mainly associated with Streptococcus abundance. Findings support a conserved association between neutrophilic asthma phenotypes and specific airway microbiota features, despite marked regional heterogeneity. 2

Core exacerbation risk pathways in severe asthma align across trials and real-world data

Bayesian networks compared 345 severe asthma patients from RCT placebo arms with 6,814 biologic‑naïve patients in ISAR. Despite greater complexity in the registry network, two core pathways to severe exacerbations were shared across settings. Total serum IgE influenced blood eosinophils, which then predicted future severe exacerbations, and prior severe exacerbation history directly predicted future events. The RCT-derived network generalized reasonably to registry patients, with an AUC of 0.68 for severe exacerbation prediction. The registry-derived network calibrated better but underperformed in trial participants, suggesting trial populations represent a constrained risk architecture. 3

CTLA-4–decorated tolerogenic VLPs induce durable, antigen-specific protection from food allergy in mice

Recombinant virus-like particles engineered to display CTLA-4 and carry defined antigens induced tolerogenic dendritic cells in vitro. These tolerogenic DCs promoted regulatory T cell activation and rendered antigen-specific effector T cells hyporesponsive. In a murine food allergy model, five consecutive daily injections of tolerogenic VLPs protected against allergic symptoms and anaphylactic shock. Protection was antigen-specific, long-lasting, and could be transferred to naïve mice via Tregs from vaccinated animals. This platform illustrates a potentially generalizable strategy for checkpoint-based, antigen-specific tolerance induction in food allergy. 4