ABSTRACT
Purpose: The purpose of this study was to investigate the production of IL-27 p28 and EBI3 in the ocular inflammatory sites, and the role of IL-27 signaling in a model of HSV-1 induced herpetic stromal keratitis (HSK). Methods: The BALB/c mice were injected intraperitoneally (24 h before infection) with anti-IL-27 antibody or IgG antibody as control, infected with HSV-1 via corneal scarification, and then injected intraperitoneally with anti-IL-27 antibody or IgG antibody at 1, 3, and 5 days postinfection. Slit lamp and histopathology were used to assess disease outcome. The levels of IL-27 p28 and EBI3 in corneas were determined by western blotting and immunofluorescence. Furthermore, viral titers were determined, and immune cell infiltrates were collected and analyzed by flow cytometry. Results: We found that the levels of IL-27 p28 and EBI3 in corneas were elevated significantly at the peak of HSK, and both of them were expressed simultaneously in the epithelium, stroma, and endothelium of corneas. In the group of anti-IL-27 treatment, the severity of the corneal lesion and CD4+ T cells infiltration were significantly decreased, and the percentage of CD4+ Foxp3+ Tregs was upregulated markedly in the spleen, DLNs and cornea of HSK mice compared to IgG treatment. Conclusion: These results provided evidence that IL-27 as a pathogenic pro-inflammatory cytokine controlled CD4+ Foxp3+ Tregs production in HSK, which ultimately resulted in promoting the progression of HSK and poor prognosis.
ABSTRACT
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.