NR1D1 mitigates IL-17a-induced small airway remodeling in biomass smoke-induced COPD

Biomass smoke (BS) exposure is a critical environmental risk factor for Chronic Obstructive Pulmonary Disease (COPD). In this study, mechanisms of biomass smoke (BS)-induced small airway disease are explored, with a focus on the roles of Interleukin-17a (IL-17a) and Nuclear Receptor Subfamily 1 Group D Member 1 (NR1D1).

This study included 20 BS exposure COPD (BS-COPD) patients and 13 controls, who underwent chest high-resolution computed tomography (HRCT) scans to assess emphysema and small airway disease. The control group was divided into a low- and high BS exposure control group. Serum IL-17a levels were measured. Wild-type and IL-17a-/- B6/C57 mice were exposed to wood smoke to establish a COPD model in mice. Airway pathology was evaluated by histological analysis. The effects of IL-17a and NR1D1 on cell proliferation of BEAS-2b cells exposed to wood smoke particulate matter 2.5 were assessed in vitro using flow cytometry and Western blotting.

HRCT revealed significantly higher small airway disease and emphysema in BS-COPD patients compared to controls (p < 0.01). Small airway disease exhibited the strongest negative correlation with FEV1%predicted (r = -0.61, p = 0.004). High-exposure control group showed significant BS Index correlations with small airway disease (r = 0.81, p = 0.049) and emphysema (r = 0.87, p = 0.025). Serum IL-17a levels correlated with small airway disease in BS-COPD (r = 0.48, p = 0.033). The mouse model demonstrated higher airway wall thickness and small airway disease in IL-17a-/- mice exposed to wood smoke. In vitro, IL-17a promoted BEAS-2b cell proliferation, an effect enhanced by NR1D1 downregulation.

BS exposure drives emphysema and small airway disease in non-COPD individuals. NR1D1 downregulation exacerbates IL-17a-mediated remodeling in vitro, suggesting therapeutic potential.

ChiCTR-OOC-16008692.