TSLP and Downstream Molecules in Experimental Mouse Allergic Conjunctivitis
TSLP and Downstream Molecules in Experimental Mouse Allergic Conjunctivitis
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DOI：
10.1167/iovs.09-4122
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
Li, De-Quan
中科院分区：
文献类型：
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作者：
Zheng, Xiaofen;Ma, Ping;Li, De-Quan
目的。使用短豚草（SRW）诱导的过敏性结膜炎（AC）小鼠模型，探讨胸腺基质淋巴细胞生成素（TSLP）及其下游分子在眼部过敏性炎症发展中的潜在作用。 BALB/c 小鼠在足垫中用 SRW 致敏后，接受 SRW 花粉的局部攻击。最后一次SRW攻击后，收获角膜上皮、结膜和颈部淋巴结，通过RT和实时PCR进行总RNA提取和基因表达，并收集整个眼球进行冷冻切片以进行免疫组织化学染色。 结果。用 SRW 过敏原反复进行局部刺激，在小鼠中产生了典型的 AC 症状。与未处理的对照组相比，SRW 诱导的 AC 小鼠的角膜和结膜上皮细胞中 TSLP mRNA 表达和免疫反应性显着增加。 CD11c(+)和OX40L(+)免疫反应细胞大量浸润结膜，角膜上皮、结膜和颈部淋巴结中检测到CD11c、TSLPR和OX40L mRNA水平增加。 AC 小鼠眼表（主要是结膜）中 CD4、IL-4、IL-5 和 IL-13 的 mRNA 和免疫反应性水平增加，并伴有 OX40、STAT6 和 GATA3 表达增加，证明了 CD4(+) Th2 细胞浸润。使用含有暴露于polyI:C的角膜上皮培养物的条件培养基的TSLP观察未成熟DC的成熟，这刺激了TSLP的产生。结论。这项研究通过产生一种新型促过敏细胞因子 TSLP，提供了关于局部粘膜上皮细胞在眼部过敏性炎症引发中的作用的新发现，TSLP 通过 TSLP-TSLPR 和 OX40L-OX40 信号通路激活树突状细胞以启动 Th2 分化和过敏性炎症。 （投资眼科可见科学。2010；51：3076-3082）DOI：10.1167/iovs.09-4122
PURPOSE. To explore the potential role of thymic stromal lymphopoietin (TSLP) and its downstream molecules in the development of ocular allergic inflammation using a short ragweed (SRW)-induced mouse model of allergic conjunctivitis (AC).METHODS. BALB/c mice were topically challenged with SRW pollen after they were sensitized with SRW in the footpad. After the last SRW challenge, the corneal epithelium, conjunctiva, and cervical lymph nodes were harvested for total RNA extraction and gene expression by RT and real-time PCR, and whole eye globes were collected to make cryosections for immunohistochemical staining.RESULTS. Repeated topical challenges with SRW allergen generated typical signs of AC in mice. Compared with the untreated controls, TSLP mRNA expression and immunoreactivity were significantly increased in the corneal and conjunctival epithelia of SRW-induced AC mice. CD11c(+) and OX40L(+) immunoreactive cells largely infiltrated the conjunctiva with increased mRNA levels of CD11c, TSLPR, and OX40L detected in the corneal epithelium, conjunctiva, and cervical lymph nodes. CD4(+) Th2 cell infiltration was evidenced by increased levels of mRNA and immunoreactivity of CD4, IL-4, IL-5, and IL-13 in the ocular surface, mainly in the conjunctiva, accompanied by increased expression of OX40, STAT6, and GATA3, in AC mice. The maturation of immature DCs was observed with the use of TSLP containing conditioned media from corneal epithelial cultures exposed to polyI:C, which stimulates TSLP production.CONCLUSIONS. This study provides new findings regarding the role of local mucosal epithelial cells in the initiation of ocular allergic inflammation by producing a novel proallergic cytokine, TSLP, which activates dendritic cells to prime Th2 differentiation and allergic inflammation through the TSLP-TSLPR and OX40L-OX40 signaling pathway. (Invest Ophthalmol Vis Sci. 2010;51:3076-3082) DOI:10.1167/iovs.09-4122