Exposure to Traffic-Related Particulate Matter 2.5 Triggers Th2-Dominant Ocular Immune Response in a Murine Model

Abstract

Ambient particulate matter (PM), a major component of air pollution, aggravates ocular discomfort and inflammation, similarly to dry eye disease (DED) or allergies. However, the mechanism(s) by which PM induces the ocular inflammatory response is unknown. This study investigated the immunological response of traffic-related fine particulate matter (PM2.5) on the ocular surface in a murine model. C57BL/6 mice were exposed by topical application to PM2.5 or vehicle for 14 days to induce experimental environmental ocular disease. Corneal fluorescein staining and the number of ocular inflammatory cells were assessed in both groups. The expression of IL-1β, IL-6, tumor necrosis factor (TNF)-α, and mucin 5AC (MUC5AC) in the ocular surface were evaluated by real-time PCR. An immunohistochemical assay evaluated apoptosis and goblet cell density. ELISA was used to determine the levels of serum IgE and cytokines of Type 1 helper (Th1) and Type 2 helper (Th2) cells after in vitro stimulation of T cells in the draining lymph nodes (LNs). Exposure to traffic-related PM2.5 significantly increased corneal fluorescein staining and cellular toxicity in the corneal epithelium compared with the vehicle control. A significant increase in the number of CD11b+ cells on the central cornea and mast cells in the conjunctiva was observed in the PM2.5 group. Exposure to PM2.5 was associated with a significant increase in the corneal or conjunctival expression of IL-1β, IL-6, TNF, and MUC5AC compared to the vehicle, and increased maturation of dendric cells (DCs) (MHC-IIhighCD11c+) in draining LNs. In addition, PM2.5 exposure increased the level of serum IgE and Th2 cytokine production in draining LNs on day 14. In conclusion, exposure to traffic-related PM2.5 caused ocular surface damage and inflammation, which induced DC maturation and the Th2-cell-dominant allergic immune response in draining LNs.

Pollen shells and soluble factors play non-redundant roles in the development of allergic conjunctivitis in mice

“…Furthermore, the skin prick test response to Asian dust has been found to correlate with the mean wheal diameters for pollens and fungi, implying its adjuvant effect [18]. Although the mechanistic studies on the effect of particulate air pollutants on the ocular surface are relatively limited [19][20][21][22][23], their biological and immunomodulatory effects on the airways have been extensively studied [24]. However, since the lower respiratory tract is accessible to only small particles with a median aerodynamic diameter under 2.5 μm, the effect of larger particles such as pollen grains onto the mucosal surface has been less characterized.…”

Air pollution and meteorological conditions significantly contribute to the worsening of allergic conjunctivitis: a regional 20-city, 5-year study in Northeast China

“…PM 2.5 has also been found to induce mast cells and eosinophilic cells infiltration into the conjunctiva in a murine model. The mast cell is known as a key immune-regulatory factor in the Th2-mediated responses, indicating PM 2.5 might trigger Th2-dominant ocular immune response 18 . In a study conducted in Tokyo, elevated level of atmosphere PM 2.5 was found to be considerably associated with an increase in numbers of outpatient visits ( r = 0.62, p = 0.018) for AC from May to July, while there seems to be no statistical significance of correlation from August to November, indicating that PM 2.5 may have played a role in AC development during the nonpollen season 19 .…”

The Protective Effect of Topical Spermidine on Dry Eye Disease with Retinal Damage Induced by Diesel Particulate Matter2.5

“…IL-17 induces the secretion of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α, and these cytokines are upregulated in DED [ 50 ]. Lee et al [ 51 ] suggested that the topical application of PM 2.5 elevated dendritic cell maturation and the expression of TNF-α, IL-1β and IL-6 in a murine model. Hyun et al [ 52 ] also reported that the expression of TNF-α and IL-6 was increased in the PM 2.5 -induced DED rat model, but extract of apricot kernel, the seed of Prunus armeniaca L. (Prunus, apricot), had a protective effect against DED by PM 2.5 .…”