Pentraxin 3 deficiency exacerbates neutrophilic inflammation and airway hyperresponsiveness in type 2-low asthma

Type 2-low asthma is a severe, steroid-resistant phenotype characterized by neutrophilic inflammation and limited treatment options. PTX3, an acute-phase protein involved in innate immunity, has been linked to inflammatory diseases; but its role in type 2-low asthma remains unclear.

A chronic HDM + c-di-GMP murine model was used to mimic type 2-low asthma. PTX3^-/- and WT mice were assessed for inflammation, cytokine profiles, antibody responses, and lung function. AHR was measured using FlexiVent. BALF inflammatory cells were analyzed by cytospin and flow cytometry. Cytokines were quantified using mesoscale assay, and serum immunoglobulins by ELISA.

In mice, the type 2-low model exhibited increased systemic and airway PTX3 levels. PTX3^-/- mice exposed to the type 2-low protocol developed significantly greater airway inflammation, with higher total BALF cell counts and a 2-fold increase in neutrophils, but no change in eosinophils. PTX3 deficiency led to increased total and HDM-specific IgE levels. BALF cytokine analysis revealed elevated IL-17A in PTX3^-/- mice, while IL-4, IL-5, and IL-13 remained unchanged. PTX3^-/- mice also exhibited significantly higher AHR parameters.

PTX3 absence enhances neutrophilic inflammation, IL-17A production, IgE responses, and AHR, highlighting PTX3 as a potential biomarker and therapeutic target in type 2- low asthma.