2026-02-11 インペリアル・カレッジ・ロンドン(ICL)
<関連情報>
- https://www.imperial.ac.uk/news/articles/medicine/nhli/2026/sex-hormones-linked-to-immune-responses-that-may-help-explain-differences-in-asthma-severity-/
- https://www.science.org/doi/10.1126/sciimmunol.adk1673
上皮成長因子受容体は、吸入アレルゲンに対する肺の2型反応における性差を制御する Epidermal growth factor receptor controls sex differences in lung type 2 responses to inhaled allergen
Helen Stölting, April L. Raftery, Simone A. Walker, Eimear N. Rutherford, […] , and Clare M. Lloyd
Science Immunology Published:23 Jan 2026
DOI:https://doi.org/10.1126/sciimmunol.adk1673
Editor’s summary
The frequency and severity of asthma are higher in adult females compared with males, and periods of hormonal change—such as puberty, pregnancy, and menopause—are associated with the modulation of symptoms. Stölting et al. report that female mice exposed to house dust mite (HDM) aeroallergens starting early in life show enhanced type 2 airway responses compared with males. The female hormone 17β-estradiol (E2) amplifies the production of interleukin-33 (IL-33) by fibroblasts. This, in turn, drives the up-regulation of epidermal growth factor receptor (EGFR) expression on T helper 2 (TH2) cells, which then boosts their secretion of T2 cytokines. EGFR may therefore serve as a bridge linking hormonal disruptions and asthma severity in females. —Seth Thomas Scanlon
Abstract
Hormonal disruptions are associated with poor asthma control in females, yet how these phenomena are linked remains unknown. Here, we investigated distinct allergen-induced immune responses between the sexes during maturation. By 6 weeks of life, female mice exposed to the aeroallergen house dust mite (HDM) from postnatal day 7 exhibited stronger type 2 (T2) immune responses and higher lung interleukin-33 (IL-33) than males. IL-33 administration to HDM-sensitized males was sufficient to augment T2 immunity and up-regulated epidermal growth factor receptor (EGFR) on T helper 2 (TH2) cells. EGFR inhibition abrogated T2 cytokine production in vitro. In vivo, EGFR inhibition reduced T2 immunity in females only, thereby abolishing any sex differences. 17β-estradiol (E2) heightened lung Il33 expression and T2 responses of HDM-sensitized males, akin to levels in females. EGFR’s ability to drive sex differences in lung T2 responses downstream of E2 and IL-33 may link hormonal disruptions to poor asthma control.
