Time-dependent analysis of bronchus-associated lymphoid tissue formation and pulmonary inflammation induced by various particulate matter in asthmatic mice model.

Particulate matter (PM) aggravates respiratory diseases, including asthma, and is associated with bronchus-associated lymphoid tissue (BALT) formation. However, the time-course effects of different PM types on pulmonary inflammation and BALT development remain unknown. Herein, we investigated the time-dependent effects of 3 PM types-titanium dioxide nanoparticles (TiO₂), diesel exhaust particles, and Asian sand dust-on lung inflammation and ectopic lymphoid tissue development over time, in the presence/absence of allergen ovalbumin. All PM types supported BALT formation, with stronger development when co-administered with ovalbumin. In allergen-treated mice, an early increase in interleukin-1α was followed by type 2 immune responses and BALT expansion. Under OVA-free conditions, despite the absence of an early interleukin-1α surge, adequate C-X-C motif chemokine ligand 1 production together with neutrophil accumulation was associated with BALT formation, particularly following repeated TiO₂ exposure. 3D lung reconstruction revealed that the progression of BALT and tertiary lymphoid structures extended from large airways to distal regions in the ovalbumin-treated groups exposed to TiO₂. TiO₂ was confirmed in the alveoli, alveolar macrophages, BALT areas, and hilar lymph nodes. These observations suggest that early elevation of interleukin-1α, adequate CXCL1 production, and neutrophil infiltration were associated with PM-induced BALT formation in a time- and context-dependent manner.