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Background: IgE‐mediated sensitisation to egg is common in infants. In some cases, the processes leading to egg sensitisation are established in early life, even before introduction to solid foods. The underlying mechanisms remain poorly understood. Methods: We performed detailed immune cell phenotyping of peripheral blood mononuclear cells and determined in vitro cytokine responses following allergen specific and non‐specific immune stimulation. To determine if unique immune profiles were linked to early‐life egg sensitisation, we compared 92 infants at 4–6 months of age, with (EggCAP+, n = 41) and without (EggCAP−, n = 51) early egg sensitisation. Additionally, 47 cord blood samples were analysed. For a subset of participants (n = 39), matching cord blood mononuclear cells were assessed by flow cytometry to establish the impact of IgE sensitisation on immune developmental trajectories. Results: EggCAP+ infants were found to exhibit a unique immune phenotype characterised by increased levels of circulating CD4+ T regulatory cells (Treg), CD4+ effector memory (EM) Treg and increased expression of the IgE receptor, FcεR1, on basophils. The increased CD4+ EM Treg profiles were already present in cord blood samples from EggCAP+ infants. A general Th2‐skewing of the immune system was observed based on increased IL‐13 production following phytohemagglutinin stimulation and by comparing immune developmental trajectories, EggCAP+ infants displayed an expansion of basophils and reduced levels of CD4− T cells compared to EggCAP− infants. Conclusions: Immunological profiles associated with egg sensitisation are detectable in infant circulation at 4–6 months of age and at birth. Understanding the immune mechanisms underlying early‐life sensitisation could provide important insights for future food allergy prevention strategies. [ABSTRACT FROM AUTHOR]

Background: The prevalence and severity of asthma, particularly the most common (atopic) form of the disease, increase amongst females but not males after puberty, and asthma activity also changes throughout the menstrual cycle and during pregnancy. The contribution of female sex hormones to asthma pathogenesis is incompletely understood. Objective: To obtain insight into the role of oestrogen (E2) in experimental atopic asthma, and guide future research on sex‐related variations in atopic asthma susceptibility/intensity in humans. Methods: We utilized an experimental model comprising rat strains expressing dichotomous Th2‐high vs Th2‐low immunophenotypes exemplified by eosinophilia, mirroring differences between human atopics/non‐atopics. We compared the efficiency of Th2‐associated immunoinflammatory mechanisms, which differed markedly between the two strains, and between sexes in the Th2‐high strain, and determined the effects of E2 administration on these differences. Results: Unique to the Th2‐high strain, eosinophil: neutrophil ratios in the airways at baseline and following sensitization/aeroallergen challenge were logfold higher in females relative to males, and this was reflected by higher baseline blood eosinophil numbers in females. Pretreatment of Th2‐high males with E2 abrogated this sex difference by selectively boosting Th2‐associated genes in the airways and eosinophilia, but was without corresponding effect in the Th2‐low strain. In contrast, parallel E2 effects on myeloid and lymphoid cell populations were relatively modest. Conclusions and Clinical Relevance: E2 acts to amplify the eosinophilic component of pre‐existing Th2‐high immunophenotype, possibly acting at the level of the common eosinophil/neutrophil precursor in bone marrow to preferentially drive eosinophil differentiation. Constitutive granulocyte profiles in which the balance between eosinophils and neutrophils is skewed towards eosinophils have been identified in independent cohort studies as markers of asthma risk, and these findings suggest that more detailed studies on the role of E2 in this context, and in relation to asthma pathogenesis in post‐pubertal females in particular, appear warranted. [ABSTRACT FROM AUTHOR]