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Social defeat stress aggravates asthma airway inflammation through neutrophils

Huan Deng¹, Xia Huang¹, Jiamin Zhang¹

¹Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Brain, Behavior, and Immunity

|November 6, 2025

Abstract

Backgrounds:

Psychological stress is a recognized contributor to asthma progression and is associated with increased neutrophils.

Objective:

To investigate the role of neutrophils and NETosis in psychosocial stress aggravates asthma airway inflammation.

Methods:

We constructed murine asthma models under social defeat stress (SDS) intervention. Wild-type,Csf3-deficient (Csf3^-/-, neutropenic), andPadi4-deficient (Padi4^-/-, impaired NETosis) mice were used to explore neutrophil-driven mechanisms.

Results:

In murine asthma models, SDS exacerbated airway hyperresponsiveness, inflammation, and remodeling. The amplified effects of SDS were attenuated in Csf3^-/- mice with neutropenia but exacerbated in neutrophilic mice. Transcriptomic analysis revealed SDS enhanced neutrophil extracellular traps (NETs) formation. Genetic inhibition of NETosis (Padi4^-/-) mitigated the SDS-induced asthma hyperresponsiveness and inflammation.

Conclusions:

Neutrophils and NETosis are critical mediators of SDS-induced asthma airway hyperresponsiveness, inflammation and mucus hypersecretion, highlighting potential therapeutic targets.

Keywords:

Asthma Neutrophil Neutrophil extracellular traps Stress

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