Social defeat stress aggravates asthma airway inflammation through neutrophils.

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.