Fukuda Ken, Kumagai Naoki, Fujitsu Youichiro, Nishida Teruo
Department of Ocular Pathophysiology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
Allergol Int. 2006 Jun;55(2):121-9. doi: 10.2332/allergolint.55.121.
Vernal keratoconjunctivitis (VKC), a severe form of ocular allergic disease, is characterized by the formation of giant papillae at the upper tarsal conjunctiva and corneal lesions that threaten vision. Recent evidence indicates that resident fibroblasts function as immune modulators in the pathogenesis of the chronic allergic inflammation associated with VKC. The T helper 2 (Th2) cell-derived cytokines interleukin (IL)-4 and IL-13 stimulate the migration and proliferation of conjunctival fibroblasts as well as protecting these cells from apoptotic cell death, effects that likely underlie the hyperplasia of fibroblasts that contributes to the formation of giant papillae. Conjunctival fibroblasts also synthesize extracellular matrix proteins and tissue inhibitors of metalloproteinases as well as down-regulate the expression of matrix metalloproteinases in response to these cytokines, effects that likely contribute to the excessive deposition of extracellular matrix that is characteristic of giant papillae. Stimulation of fibroblasts in the corneal stroma with the combination of a proinflammatory cytokine and either IL-4 or IL-13 results in up-regulation of the expression of the chemokine eotaxin and thymus- and activation-regulated chemokine as well as of vascular cell adhesion molecule-1, which together mediate the infiltration and activation of eosinophils and Th2 cells. Fibroblasts therefore appear to play a central role in the induction and amplification of ocular allergic inflammation and the consequent development of giant papillae and corneal disorders in individuals with VKC. Fibroblasts and fibroblast-derived factors thus represent new and potentially important therapeutic targets for treatment of the giant papillae and corneal disorders associated with VKC.
春季角结膜炎（VKC）是一种严重的眼部过敏性疾病，其特征是在上睑结膜形成巨大乳头以及出现威胁视力的角膜病变。最近的证据表明，驻留的成纤维细胞在与VKC相关的慢性过敏性炎症的发病机制中起免疫调节作用。辅助性T细胞2（Th2）细胞衍生的细胞因子白细胞介素（IL）-4和IL-13刺激结膜成纤维细胞的迁移和增殖，并保护这些细胞免于凋亡性细胞死亡，这些作用可能是导致促成巨大乳头形成的成纤维细胞增生的基础。结膜成纤维细胞还合成细胞外基质蛋白和金属蛋白酶组织抑制剂，并响应这些细胞因子而下调基质金属蛋白酶的表达，这些作用可能导致巨大乳头特征性的细胞外基质过度沉积。用促炎细胞因子与IL-4或IL-13联合刺激角膜基质中的成纤维细胞会导致趋化因子嗜酸性粒细胞趋化蛋白和胸腺与活化调节趋化因子以及血管细胞黏附分子-1的表达上调，它们共同介导嗜酸性粒细胞和Th2细胞的浸润和活化。因此，成纤维细胞似乎在眼部过敏性炎症的诱导和放大以及VKC患者随之出现的巨大乳头和角膜疾病的发展中起核心作用。成纤维细胞和成纤维细胞衍生因子因此代表了治疗与VKC相关的巨大乳头和角膜疾病的新的且可能重要的治疗靶点。
