Traffic-related particulate matter aggravates ocular allergic inflammation by mediating dendritic cell maturation

The aim of this study was to determine the effects of traffic-related particulate matter (PM) on allergic inflammation of ocular surfaces. BALB/c mice were sensitized with ovalbumin (OVA) and aluminum hydroxide via intraperitoneal injection. Two weeks later, mice were challenged with eye drops containing OVA concomitant with either traffic-related PM_2.5 or vehicle eye drops. Topical OVA challenges were administered following unilateral subconjunctival injection of magnetic-bead-sorted CD11c+ dendritic cells (DC). The following were assessed: (1) clinical signs, (2) infiltration of inflammatory cells into conjunctiva, (3) serum levels of OVA-specific IgE production, and (4) T-cell cytokine secretion with topical application of PM_2.5, compared to saline vehicle. PM_2.5 was found to increase production of OVA-specific IgE in serum and Th2 immune response-related cytokines including interleukin (IL)-4, IL-17A, and IL-13 compared to vehicle control. It is of interest that PM_2.5 treatment also elevated the population of mature DCs in draining lymph nodes (LNs). Exposure with PM_2.5 was associated with a significant rise in conjunctival expression of IL-1β, IL-6, IL-17, and TNF. After subconjunctival injection of CD11c+DCs from PM_2.5-treated allergic conjunctivitis (AC) mice into naïve mice, T cell responses and OVA-specific IgE were also enhanced. Data suggest that traffic-related PM_2.5 exacerbated allergic conjunctivitis as evidenced by increased infiltration of inflammatory cells into the conjunctiva and Th2 responses in the draining LNs associated with enhanced maturation of DCs. Our findings provide new insight into the hazardous potential of traffic-related PM_2.5 on allergic diseases, such as asthma or atopic dermatitis.本研究旨在明确交通相关颗粒物（particulate matter, PM）对眼表变应性炎症的影响。实验选用BALB/c小鼠，通过腹腔注射卵清蛋白（ovalbumin, OVA）联合氢氧化铝进行致敏。两周后，小鼠经眼滴给药，分别给予含OVA联合交通相关PM₂.₅的滴眼液，或仅含载体的对照滴眼液。同时，在单侧结膜下注射磁珠分选的CD11c⁺树突状细胞（dendritic cell, DC）后，予以局部OVA激发。本研究评估了以下四项指标：(1) 临床体征；(2) 结膜炎症细胞浸润情况；(3) 血清OVA特异性IgE水平；(4) 局部应用PM₂.₅与生理盐水载体对照相比时的T细胞细胞因子分泌水平。研究发现，与载体对照组相比，PM₂.₅可升高血清中OVA特异性IgE的产生量，并增强包括白细胞介素（interleukin, IL）-4、IL-17A及IL-13在内的Th2免疫应答相关细胞因子的表达。值得关注的是，PM₂.₅处理还可增加引流淋巴结（lymph node, LN）中成熟树突状细胞的数量。PM₂.₅暴露可显著上调结膜组织中IL-1β、IL-6、IL-17及TNF的表达水平。将经PM₂.₅处理的变应性结膜炎（allergic conjunctivitis, AC）小鼠的CD11c⁺DCs结膜下注射至未致敏小鼠体内后，后者的T细胞应答及OVA特异性IgE水平同样得到增强。实验数据表明，交通相关PM₂.₅可加重变应性结膜炎，其证据为结膜炎症细胞浸润增加，以及伴随树突状细胞成熟增强的引流淋巴结内Th2应答升高。本研究结果为交通相关PM₂.₅对哮喘、特应性皮炎等变应性疾病的潜在危害提供了新的见解。