This report deals with the possible mechanism by which IL-18 can contribute to the control and resolution of inflammatory lesions in the cornea caused by herpes simplex virus infection. Our results demonstrate that the expression of the IL-18R by both regulatory T cells (Treg) and effector T cells was a pivotal event that influenced lesion pathogenesis. The engagement of IL-18R on Treg with its cytokine ligand resulted in Amphiregulin expression a molecule associated with tissue repair. In support of this scheme of events, lesion severity became more severe in animals unable to express the IL-18R because of gene knockout and was reduced in severity when IL-18 was overexpressed in the cornea. These changes in lesion severity correlated with the frequency and number of both Treg and Teff that expressed Amphiregulin. Additional experiments indicated that IL-12 and IL-18 acted synergistically to enhance Amphiregulin expression in Treg, an event partly dependent on P38 MAPK activity. Finally, sub-conjunctival administration of Amphiregulin resulted in resolution of both developing and developed lesions. Thus, overall our results imply that IL-18 may participate in controlling the severity of SK and contribute to tissue repair by converting both Treg and effector T cells into those that produce Amphiregulin.

中文翻译：

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IL-18 诱导的双调蛋白表达对病毒诱导的眼部病变的作用。

本报告探讨了 IL-18 有助于控制和消退由单纯疱疹病毒感染引起的角膜炎性病变的可能机制。我们的结果表明，调节性 T 细胞 (Treg) 和效应 T 细胞表达 IL-18R 是影响病变发病机制的关键事件。Treg 上的 IL-18R 与其细胞因子配体的结合导致双调蛋白表达，这是一种与组织修复相关的分子。为了支持这一事件方案，由于基因敲除而无法表达 IL-18R 的动物的病变严重程度变得更加严重，并且当 IL-18 在角膜中过度表达时，严重程度降低。病变严重程度的这些变化与表达双调蛋白的 Treg 和 Teff 的频率和数量相关。其他实验表明 IL-12 和 IL-18 协同作用以增强 Treg 中双调蛋白的表达，该事件部分依赖于 P38 MAPK 活性。最后，双调蛋白的结膜下给药导致发展中和发展中的病变消退。因此，总的来说，我们的结果表明 IL-18 可能参与控制 SK 的严重程度，并通过将 Treg 和效应 T 细胞转化为产生双调蛋白的细胞来促进组织修复。