IL33 contributes to diesel pollution-mediated increase in experimental asthma severity

Area of Science:

• Immunology
• Pulmonology
• Environmental Health

Background:

• Traffic pollution, specifically diesel exhaust particles (DEP), is linked to increased asthma risk and exacerbations.
• The role of cytokines like IL-25, IL-33, and TSLP from stressed lung cells in DEP-induced asthma severity is not well understood.

Purpose of the Study:

• To investigate the contribution of IL-33 signaling to diesel exhaust particle (DEP)-induced asthma severity.
• To explore the role of the IL-33 receptor ST2 in mediating airway hyper-responsiveness and inflammation in response to DEP and allergen co-exposure.

Main Methods:

• BALB/c mice were exposed to DEP and/or house dust mite extract (HDM).
• Airway hyper-responsiveness, pulmonary inflammation, and T-cell subsets were assessed in mice with normal or deficient ST2 expression.
• In vitro studies examined cytokine secretion from lung cells and bone marrow-derived dendritic cells (BMDCs) following HDM and/or DEP exposure.

Main Results:

• DEP exposure alone induced oxidative stress and IL-6 but not allergic features; co-exposure with HDM increased IL-33 and Th2 responses.
• ST2 deficiency partially protected against HDM + DEP-induced airway hyper-responsiveness and type 2 inflammation.
• IL-33 signaling in dendritic cells and T-cells was crucial for HDM + DEP-induced cytokine secretion (IL-5, IL-13, IL-6, IL-17A) and mixed Th2/Th17 responses.

Conclusions:

• IL-33 contributes to DEP-enhanced allergen-induced Th2 inflammation and airway hyper-responsiveness in a severe asthma mouse model.
• This effect may involve the accumulation of pathogenic IL-5+ IL-17A+ CD4+ effector T-cells.
• Targeting IL-33 signaling could be a potential therapeutic strategy for severe, steroid-resistant asthma exacerbated by traffic pollution.