PM2.5 Stimulates Macrophage-Derived Thymic Stromal Lymphopoietin (TSLP) to Induce a Mouse Model of Allergic Conjunctivitis

Increasing epidemiologic evidence has indicated that PM2.5 exposure is strongly correlated with the prevalence of allergic conjunctivitis (AC), but there is no experimental model for elucidating the underlying mechanism involved. We established a stable PM2.5-induced mouse model of AC to explore the adverse effects of PM2.5 on the ocular surfaces and the underlying mechanisms involved. BALB/c mice were sensitized by intraplanar injection of 200 μg PM2.5 on day 0 and challenged for 10 consecutive days, beginning on day 9, with eye drops containing 12.5 mg/mL PM2.5. Assessments of the ocular surfaces, eye blink counts, and tear secretion were performed to evaluate clinical symptoms. The whole eyes were harvested for histopathological and immunofluorescence analyses, the conjunctiva was isolated for Western blotting, and the sera were subjected to IgE ELISA to evaluate the immune characteristics and TSLP-related pathway expression. Furthermore, mouse bone marrow-derived macrophages (BMDMs) were incubated with 25 μg/mL PM2.5 for 24 h. Cellular protein and RNA were extracted for Western blotting and RNA sequencing. PM2.5 exposure induced clinical manifestations and pathological changes similar to those in human AC. The sensitization and challenge evoked Th2 responses and serum IgE production. PM2.5 exposure mediated TSLP production in macrophages and aggravated allergic inflammation through the TSLP-TSLPR and TSLP-OX40L signaling pathways in vivo. Macrophages produced TSLP and polarized to the M1 phenotype after PM2.5 administration in vitro. These results demonstrate a reproducible method for establishing a PM2.5-induced AC model. In addition, PM2.5 exposure stimulated macrophages to secrete TSLP and enhance allergic inflammation.