Chung So-Hyang, Chang Sun Young, Lee Hyun Jung, Choi Seong Hyun
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; Catholic Institute of Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon, Kyeonggi-do, Korea.
Clin Immunol. 2015 Dec;161(2):110-9. doi: 10.1016/j.clim.2015.08.004. Epub 2015 Aug 22.
Allergic conjunctivitis from an allergen-driven Th2 response is characterized by conjunctival eosinophilic infiltration. Although CCL20-CCR6 axis has been reported to play a proinflammatory role in several murine models of autoimmune diseases including allergic diseases, their underlying mechanism needs to be investigated. We here examined whether CCL20-CCR6 axis could play a role in the development of allergic conjunctival inflammation using murine experimental allergic conjunctivitis (EAC) model induced by ovalbumin (OVA) allergen. Mice were challenged with consecutive 10days of OVA via conjunctival sac after systemic challenge with OVA and cholera toxin in alum. Several indicators for allergy were comparatively evaluated in wild-type and CCR6 KO EAC mice. Wild-type mice challenged with OVA via conjunctival sac following systemic challenge with OVA in alum had severe allergic conjunctivitis. The absence of CCR6 suppressed IgE secretion and allergic conjunctival inflammation. Reduced allergic inflammation was ascribable to reduced cytokine responses from Th-2 type in draining lymph node although Th17, regulatory T cells and dendritic cell subsets are not affected by the absence of CCR6. In addition, neutralization of CCR6 ligand, CCL20 could repress allergic conjunctival inflammation. Our findings suggested that CCR6 might be crucial for optimal development of Th2 immune responses and further allergic conjunctival inflammation in EAC model.
由变应原驱动的Th2反应引起的过敏性结膜炎的特征是结膜嗜酸性粒细胞浸润。尽管据报道CCL20-CCR6轴在包括过敏性疾病在内的几种自身免疫性疾病的小鼠模型中发挥促炎作用,但其潜在机制仍需研究。我们在此使用卵清蛋白(OVA)变应原诱导的小鼠实验性变应性结膜炎(EAC)模型,研究CCL20-CCR6轴是否在变应性结膜炎症的发展中起作用。在用OVA和明矾中的霍乱毒素进行全身激发后,通过结膜囊连续10天用OVA对小鼠进行激发。在野生型和CCR6基因敲除的EAC小鼠中比较评估了几种过敏指标。在用明矾中的OVA进行全身激发后,通过结膜囊用OVA激发的野生型小鼠患有严重的变应性结膜炎。CCR6的缺失抑制了IgE分泌和变应性结膜炎症。变应性炎症减轻归因于引流淋巴结中Th2型细胞因子反应的降低,尽管Th17、调节性T细胞和树突状细胞亚群不受CCR6缺失的影响。此外,中和CCR6配体CCL20可抑制变应性结膜炎症。我们的研究结果表明,CCR6可能对EAC模型中Th2免疫反应的最佳发展以及进一步的变应性结膜炎症至关重要。