Microplastics drives ILC2s function and fatty acid metabolism in allergic airway inflammation via PPARγ signaling

Area of Science:

• Environmental Health
• Immunology
• Toxicology

Background:

• Microplastics (MPs) are emerging airborne pollutants found in human lungs.
• Their role in allergic airway inflammation and pathogenic mechanisms is not well understood.
• MPs are increasingly recognized as potential drivers of respiratory diseases.

Purpose of the Study:

• To investigate the role of MPs in exacerbating allergic airway inflammation.
• To elucidate the underlying pathogenic mechanisms, focusing on immune activation and epithelial barrier function.
• To identify potential therapeutic targets for MP-induced lung impairment.

Main Methods:

• House dust mite (HDM)-sensitized mouse model of allergic airway inflammation.
• Exposure to microplastics (MPs) and assessment of inflammatory markers.
• Analysis of epithelial barrier integrity, immune cell populations (ILC2s), and cytokine profiles (IL-33, IL-5, IL-13).
• Investigation of Peroxisome proliferator-activated receptor gamma (PPARγ) expression and function in epithelial-ILC2 co-cultures.
• Pharmacological inhibition of PPARγ to assess its therapeutic potential.

Main Results:

• MPs exposure exacerbated allergic airway inflammation in HDM-sensitized mice.
• MPs promoted epithelial barrier disruption and type 2 immune activation, increasing IL-33 release and ILC2s.
• PPARγ was upregulated in ILC2s, driving metabolic reprogramming (fatty acid uptake, lipid droplet accumulation) and fueling ILC2 activation.
• Pharmacological inhibition of PPARγ attenuated MP-induced allergic airway inflammation.

Conclusions:

• MPs aggravate allergic airway inflammation through an epithelial-PPARγ-ILC2s axis.
• MPs induce immunometabolic reprogramming in ILC2s via PPARγ, contributing to lung impairment.
• Targeting the PPARγ pathway presents a potential therapeutic strategy for microplastic-induced respiratory diseases.