Zhang Zong-Duan, Deng Yu-Xuan, Ma Hui-Xiang, Chen Xiao-Gang, Chen Lin-Hua, Qu Jia
Eye Hospital of Wenzhou Medical University, Wenzhou, China.
Cornea. 2019 Mar;38(3):344-351. doi: 10.1097/ICO.0000000000001832.
To investigate the expression of thymic stromal lymphopoietin (TSLP) and the relevant signaling pathways in the giant papillae obtained from patients with vernal keratoconjunctivitis (VKC) and to study the potential functional role and molecular mechanism of TSLP.
Giant papillae from VKC patients and control samples were used to perform immunohistochemical staining and analyze the mRNA expression of TSLP and related pathway by real-time polymerase chain reaction.
TSLP was markedly expressed in the epithelial cells and some inflammatory cells of giant papillae, but not in the control conjunctival tissue. TSLP mRNA expression in the giant papillae of VKC was increased by 9.63 ± 0.99 (mean ± SD) fold compared with controls (P < 0.01). CD11c and OX40L immunoreactive cells largely infiltrated the giant papillae as observed by immunohistochemical staining. CD4Th2 cell infiltration was observed through high immunoreactivity of CD4. Th2 cytokines (IL-4, IL-5 and IL-13) and OX40 in the VKC specimens showed increased expression. Augmented gene expression levels of CD4 (6.88 ± 1.84), OX40L (7.60 ± 1.79), OX40 (7.25 ± 1.38), IL-4 (6.89 ± 1.46), IL-5 (8.42 ± 1.55), and IL-13 (9.69 ± 1.94) were significantly different from controls (P < 0.05).
Our observations provide strong evidence that TSLP may be a crucial factor that contributes to the development and progression of allergic conjunctivitis. The results also demonstrated that TSLP activates dendritic cells to prime CD4T cells to differentiate into Th2 type and triggers Th2-dominant allergic inflammation through the TSLP/OX40L/OX40 signaling as part of immunopathogenesis of VKC.
研究春季角结膜炎(VKC)患者巨大乳头中胸腺基质淋巴细胞生成素(TSLP)的表达及其相关信号通路,探讨TSLP的潜在功能作用和分子机制。
采用VKC患者的巨大乳头和对照样本进行免疫组织化学染色,并通过实时聚合酶链反应分析TSLP及相关通路的mRNA表达。
TSLP在巨大乳头的上皮细胞和一些炎症细胞中显著表达,而在对照结膜组织中不表达。VKC巨大乳头中TSLP mRNA表达较对照组增加了9.63±0.99(平均值±标准差)倍(P<0.01)。免疫组织化学染色观察到CD11c和OX40L免疫反应性细胞大量浸润巨大乳头。通过CD4的高免疫反应性观察到CD4Th2细胞浸润。VKC标本中Th2细胞因子(IL-4、IL-5和IL-13)和OX40表达增加。CD4(6.88±1.84)、OX40L(7.60±1.79)、OX40(7.25±1.38)、IL-4(6.89±1.46)、IL-5(8.42±1.55)和IL-13(9.69±1.94)的基因表达水平与对照组相比有显著差异(P<0.05)。
我们的观察结果提供了有力证据,表明TSLP可能是导致过敏性结膜炎发生和发展的关键因素。结果还表明,TSLP激活树突状细胞使CD4T细胞分化为Th2型,并通过TSLP/OX40L/OX40信号触发以Th2为主的过敏性炎症,这是VKC免疫发病机制的一部分。