On the role of retinoic acid in virus induced inflammatory response in cornea

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.