Objective:

To summarize the impact of estrogen and various immune and inflammatory cell types on asthma phenotypes in females.

Approach:

• Epidemiological Patterns: Asthma shows sex differences, with higher prevalence in males during childhood and in females after puberty.
• Estrogen's Role: Estrogen, particularly 17β-estradiol (E2), is a key regulator of immune responses and asthma heterogeneity.
• Receptor Mechanisms: Estrogen receptors (ERα and ERβ) mediate distinct immunological effects, with ERα promoting immune activation and ERβ providing anti-inflammatory functions.
• Influencing Factors: Asthma phenotypes in females are influenced by hormonal signaling, obesity, comorbidities, viral infections, and environmental pollutants.

Key Findings:

• Adult females exhibit a higher prevalence of non-type 2 inflammation compared to males.
• Estrogen's effects on immunity are context-dependent, influenced by receptor subtype and hormone concentration.
• Sex chromosome-linked mechanisms contribute to immune activation in females.

Interpretation:

The review highlights the complexity of estrogen's role in asthma and the need for precision strategies that consider hormonal and life-stage differences.

Limitations:

• Direct evidence linking estrogen's immunological actions specifically to asthma is limited.
• The review primarily focuses on 17β-estradiol, which may not generalize to other estrogens.

Conclusion:

Understanding estrogen's role in asthma can inform future research and therapeutic strategies.