CD160/BTLA-HVEM-LIGHT/LT-α共信号通路与单纯疱疹病毒性角膜基质炎的研究

Role of CD160/BTLA-HVEM-LIGHT/LT-α signaling pathway related to herpetic stromal keratitis

单纯疱疹病毒性角膜基质炎（HSK）是主要由CD4^＋ T细胞介导的免疫病理性疾病，是可致盲的角膜感染性疾病之一。单纯疱疹病毒（HSV）进入介导子（HVEM）又名TNFRSF14，在病毒感染时可以通过病毒表面糖蛋白D（gD）介导HSV进入细胞。目前研究证实存在5种配体与HVEM结合，分别为HSV-gD、BALT、CD160、LIGHT和淋巴毒素α（LT-α）。HSV-gD与HVEM结合能够促进病毒包膜与细胞的融合，介导病毒在细胞间的扩散和释放。在T细胞的活化和增生中，HVEM-LIGHT/LT-α提供协同刺激信号，HVEM-BTLA/CD160提供协同抑制信号，此双向作用使HVEM成为一个＂分子开关＂，共同调节机体免疫应答。本文分别阐述HVEM通过与不同的配体结合所发挥不同的生物学作用，并结合CD160/BTLA-HVEM-LIGHT/LT-α共信号通路在HSK的相关实验研究，深入了解HSK的发病机制，并为HSK的有效治疗提供思路。通过有效的临床干预降低炎性免疫反应，从而达到对自身免疫性疾病的复发和慢性免疫性疾病的治疗作用。

Ocular infection of herpes simplex virus-1 （HSV1） can result in herpetic stromal keratitis （HSK）, which impairs vision and is a common cause of human blindness.Studies indicated that HSK lesions are mainly orchestrated by CD4^＋ T cells.Herpesvirus entry mediator （HVEM）, a tumor necrosis factor receptor superfamily member, facilitates virus entry through interactions with viral glycoprotein D （gD）. HVEM, a widely expressed tumor necrosis factor （TNF） receptor superfamily member with diverse roles in immune signaling.Intriguingly, HVEM has five receptors： two costimulatory molecules （LIGHT and LT-α）, two coinhibitory molecules （BTLA and CD160）, and the HSV-gD.HVEM is referred to as a molecular switch because of its capacity to deliver costimulatory signals when bound to LIGHT/LT-α and to produce inhibitory signals when bound to BTLA/CD160.In this paper, the researching progress of the five receptors functions of HVEM and CD160/BTLA-HVEM-LIGHT/LT-α signaling pathway in the HSK were reviewed.We have to provide an insight into the pathogenesis of HSK and clinical ideas for the effective treatment of HSK.Through effective clinical intervention, the inflammatory immune response is reduced, thereby achieving therapeutic effects on recurrence of autoimmune diseases and chronic immune diseases.