Oestrogen amplifies pre‐existing atopy‐associated Th2 bias in an experimental asthma model
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".