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Updated: May 15, 2025
Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
PM2.5 Stimulates Macrophage-Derived Thymic Stromal Lymphopoietin (TSLP) to Induce a Mouse Model of Allergic
Yazhou Qin1,2, Yue Bian1,2, Jingbo Hu1
1Department of Ophthalmology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Exposure to fine particulate matter (PM2.5) causes allergic conjunctivitis (AC) by stimulating macrophages to release TSLP, worsening eye inflammation. This study presents a new mouse model for AC research.
Area of Science:
- Ophthalmology
- Environmental Health
- Immunology
Background:
- Epidemiologic studies link PM2.5 exposure to allergic conjunctivitis (AC).
- Mechanisms underlying PM2.5-induced AC remain unclear.
- A robust experimental model is needed to study AC pathogenesis.
Purpose of the Study:
- Establish a stable mouse model of PM2.5-induced AC.
- Investigate the effects of PM2.5 on ocular surfaces.
- Elucidate the underlying mechanisms of PM2.5-induced AC.
Main Methods:
- BALB/c mice were sensitized and challenged with PM2.5.
- Clinical symptoms, ocular surface changes, and tear secretion were assessed.
- Histopathology, immunofluorescence, IgE ELISA, Western blotting, and RNA sequencing were performed.
Main Results:
- PM2.5 exposure induced AC-like clinical and pathological changes.
- Th2 responses and IgE production were observed.
- PM2.5 stimulated TSLP production in macrophages, activating TSLP-TSLPR and TSLP-OX40L pathways, leading to M1 polarization.
Conclusions:
- A reproducible PM2.5-induced AC mouse model was established.
- PM2.5 exposure promotes TSLP secretion by macrophages.
- This enhances allergic inflammation via specific signaling pathways.
