title: Suppressor of cytokine signaling 1 (SOCS1) mitigates anterior uveitis and confers protection against ocular HSV-1 infection.
abstract: 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.
authors.affiliation: Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Building 10, Room 10N109A, 10 Center Drive, Bethesda, MD, 20892-1857, USA.
authors.forename: Cheng-Rong
authors.initials: CR
authors.lastname: Yu
authors.forename: Kozaburo
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yun Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Rashid M
authors.initials: RM
authors.lastname: Mahdi
authors.forename: De Fen
authors.initials: DF
authors.lastname: Shen
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Charles E
authors.initials: CE
authors.lastname: Egwuagu
mesh_terms: D000818:Animals; D004731:Endotoxins; D015828:Eye Infections, Viral / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D050794:STAT1 Transcription Factor / Q000235:genetics*; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity; D015398:Signal Transduction / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics*; D058504:Th17 Cells / Q000276:immunology; D014606:Uveitis, Anterior / Q000276:immunology* / Q000382:microbiology / Q000821:virology
chemical_list: D004731:Endotoxins; D050794:STAT1 Transcription Factor; C491590:Socs1 protein, mouse; C491589:Socs1 protein, rat; C494080:Stat1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma