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Sex Differences in Asthma Pathogenesis
Kaitlin E McKernan1,2, Emely Henriquez Pilier1,2, Dawn C Newcomb1,2
1Department of Pathology, Microbiology, and Immunology, Center for Vanderbilt Immunobiology, Nashville, Tennessee, USA.
Immunological Reviews
|January 9, 2026
Summary
Sex hormones significantly impact asthma development and severity throughout life. Understanding these sex differences is crucial for developing personalized asthma treatments for males and females.
Area of Science:
- Immunology
- Endocrinology
- Respiratory Medicine
Background:
- Asthma prevalence and morbidity exhibit sex-based differences that evolve across the lifespan.
- Sex hormone signaling pathways are implicated in asthma pathogenesis, influencing airway inflammation.
- Existing research utilizes human studies, cell cultures, and animal models to explore these connections.
Purpose of the Study:
- To elucidate the specific roles of androgens and estrogens in asthma.
- To investigate the impact of sex hormones on different types of airway inflammation.
- To identify knowledge gaps regarding sex differences in asthma during reproductive stages and childhood.
Main Methods:
- Analysis of large human cohorts.
- In vitro studies using human cells.
- Experimental investigations in animal models.
Main Results:
- Androgens were found to reduce airway inflammation, including type 2 inflammation and eosinophil infiltration.
- Androgens also decreased neutrophil-induced airway inflammation in animal models.
- Estrogen signaling via ER-α was linked to increased IL-33 production, exacerbating type 2 inflammation and neutrophilic inflammation via Th17 cells.
Conclusions:
- Sex hormones play a significant, often opposing, role in modulating airway inflammation in asthma.
- Further research is required to understand asthma control during pregnancy and menopause in women.
- Investigating sex differences in immune cell development and airway inflammation is key to understanding childhood asthma onset and incidence.
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