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Immunological responses to pathogens are stringently regulated in the eye to prevent excessive inflammation that damage ocular tissues and compromise vision. Suppressors of cytokine signaling (SOCS) regulate intensity/duration of inflammatory responses. We have used SOCS1-deficient mice and retina-specific SOCS1 transgenic rats to investigate roles of SOCS1 in ocular herpes simplex virus (HSV-1) infection and non-infectious uveitis. We also genetically engineered cell-penetrating SOCS proteins (membrane-translocating sequence (MTS)-SOCS1, MTS-SOCS3) and examined whether they can be used to inhibit inflammatory cytokines. Overexpression of SOCS1 in transgenic rat eyes attenuated ocular HSV-1 infection while SOCS1-deficient mice developed severe non-infectious anterior uveitis, suggesting that SOCS1 may contribute to mechanism of ocular immune privilege by regulating trafficking of inflammatory cells into ocular tissues. Furthermore, MTS-SOCS1 inhibited IFN-γ-induced signal transducers and activators of transcription 1 (STAT1) activation by macrophages while MTS-SOCS3 suppressed expansion of pathogenic Th17 cells that mediate uveitis, indicating that MTS-SOCS proteins maybe used to treat ocular inflammatory diseases of infectious or autoimmune etiology. [ABSTRACT FROM AUTHOR]

Helper T (Th) cells comprising Th1, Th2, Th17, and Treg are involved in the pathogenesis of various vascular inflammations, and information about Th cells in Henoch-Schonlein purpura (HSP) is still controversial. The aim of our study was to investigate the changes in CD4 T cell subsets and their roles in the pathogenesis of HSP. Thirty children with diagnosis of HSP and thirty age-matched healthy controls were enrolled in this study. Real-time PCR was used to evaluate the mRNA expression levels of transcriptional factors and cytokines of CD4 T cells. Proportions of Th1, Th2, Th17, and Treg cells in peripheral blood were detected by flow cytometry. Plasma cytokine concentrations were measured by ELISA. The proportions of Th2 and Th17 cells increased significantly in children with acute HSP ( P < 0.05), while there were no significant differences between HSP and healthy controls regarding the proportions of Treg cells and Th1 cells ( P > 0.05). mRNA levels of transcriptional factors and cytokines of Th2 and Th17 cells were significantly up-regulated ( P < 0.05), while the differences were not significant as to those of Th1 and Treg cells ( P > 0.05). Plasma concentrations of IL-17A, IL-4, and IL-6 in patients with HSP were found to be much higher than those of the control group ( P < 0.05), and no differences between IFN-γ, IL-12, and TGF-β were detected between the two groups ( P > 0.05). Presence of higher proportions of Th2 and Th17 cells in patients with HSP could be closely correlated with aberrant creation of antibody and development of vessel vasculitis. The changes in cytokine milieu in peripheral blood may play an important role in the derangement of CD4 T cell subset. [ABSTRACT FROM AUTHOR]