On the role of retinoic acid in virus induced inflammatory response in cornea
On the role of retinoic acid in virus induced inflammatory response in cornea
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DOI：
10.1016/j.micinf.2018.04.007
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发表时间：
2018-06-01
影响因子：
5.8
通讯作者：
Rouse, Barry T.
中科院分区：
文献类型：
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作者：
Jaggi, Ujjaldeep;Varanasi, Siva Karthik;Rouse, Barry T.
眼部感染单纯疱疹病毒（HSV）可导致慢性免疫炎性病变，这是人类失明的重要原因。控制间质角膜炎（SK）病变严重程度的关键是确定导致组织损伤的细胞和分子事件并对其进行抵消。实现这种治疗的一种潜在有效方法是维甲酸（RA）。本研究表明，RA治疗通过抑制负责协调SK的T效应亚型来降低SK的严重程度。RA还有助于稳定调节性T细胞（Treg）的功能，从而抵消炎症细胞的活性。体外研究证实了Treg的稳定作用，当暴露于IL-12和il - 6+ tgf - β等促炎条件时，RA显示保留Foxp3表达。体内研究表明，RA通过下调HSV-1感染后Treg上IL-6R的表达来发挥稳定作用，这有助于控制SK的进展。由于该疗法在病变开始早期和之后都有效，因此它可能是一种有价值的治疗手段，无论是单独使用还是与其他疗法一起使用。(C) 2018年巴斯德研究所。Elsevier Masson SAS出版。版权所有。
Ocular infection with herpes simplex virus (HSV) can result in a chronic immune inflammatory lesion that is a significant cause of human blindness. A key to controlling stromal keratitis (SK) lesion severity is to identify cellular and molecular events responsible for tissue damage and to counteract them. One potentially useful approach to achieve such therapy is Retinoic Acid (RA). Here we show that RA therapy reduces the severity of SK by having inhibitory effects on the T effector subtypes responsible for orchestrating SK. RA also served to stabilize the function of regulatory T cell (Treg) which counteract inflammatory cell activity. The Treg stabilizing effect was demonstrated by in vitro studies where RA was shown to retain Foxp3 expression when exposed to pro-inflammatory conditions such as IL-12 and IL6+TGF-beta. in vivo studies revealed that RA exerted its stabilizing effects by downregulating IL-6R expression on Treg after HSV-1 infection and this helped to control the progression of SK. Since the therapy was effective when used both early and after the initiation of lesions, it may represent a valuable means of therapy when used alone or along with additional therapies. (C) 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.