‘Role of IL-28A in Herpes Stromal Keretitis’.

Abstract

Abstract 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 SK lesion severity is to identify cellular and molecular events responsible for tissue damage. Interferons are key cytokines in the establishment of a multifaceted antiviral response. Although all IFNs are important mediators of antiviral protection, their roles in antiviral defence vary. Interferon lambda which is a type III cytokine is capable of inducing an antiviral response both in vitro as well as in vivo. This family consists of three structurally related interferon lambda subtypes called IFN-λ (IL-29), IFN-λ2 (IL-28A) and IFN-λ3 (IL-28B). Here, we show that IFN-λ2 (IL-28A) has a prominent role in HSK. The binding of IFN-λ to their cognate receptors induces a common signaling cascade that results in the activation of STAT1 and STAT2, which promotes MX1, OAS1 and IRF7 which in turn mediate the antiviral activity of the type-III IFNs. Here we show that IL-28A appears to specifically target neutrophil function and cause a major reduction in the total number of CD4 and γδT cells and also in TH17 cells in DLN. Also, we found that the serum levels of IL-1β were reduced at the early stage of treatment. Administration of IL-28A effectively reduces the HSK lesions and can prove to be a very reliable therapeutic agent.