SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis)
Uveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation of pathogenic Th1 and Th17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR) that inhibits JAK2/STAT1 pathways...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/2939370 |
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| author | Chang He Cheng-Rong Yu Mary J. Mattapallil Lin Sun Joseph Larkin III Charles E. Egwuagu |
| author_facet | Chang He Cheng-Rong Yu Mary J. Mattapallil Lin Sun Joseph Larkin III Charles E. Egwuagu |
| author_sort | Chang He |
| collection | DOAJ |
| description | Uveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation of pathogenic Th1 and Th17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR) that inhibits JAK2/STAT1 pathways has recently been shown to suppress experimental autoimmune uveitis (EAU). However, it is not clear whether SOCS1-KIR ameliorated uveitis by targeting JAK/STAT pathways of pathogenic lymphocytes or via inhibition of macrophages and antigen-presenting cells that also enter the retina during EAU. To further investigate mechanisms that mediate SOCS1-KIR effects and evaluate the efficacy of SOCS1-KIR as an investigational drug for chronic uveitis, we induced EAU in rats by adoptive transfer of uveitogenic T-cells and monitored disease progression and severity by slit-lamp microscopy, histology, and optical coherence tomography. Topical administration of SOCS1-KIR ameliorated acute and chronic posterior uveitis by inhibiting Th17 cells and the recruitment of inflammatory cells into retina while promoting expansion of IL-10-producing Tregs. We further show that SOCS1-KIR conferred protection of resident retinal cells that play critical role in vision from cytotoxic effects of inflammatory cytokines by downregulating proapoptotic genes. Thus, SOCS1-KIR suppresses uveitis and confers neuroprotective effects and might be exploited as a noninvasive treatment for chronic uveitis. |
| format | Article |
| id | doaj-art-3228f2af3c6f46a3b189c8e583648fb8 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-3228f2af3c6f46a3b189c8e583648fb82025-08-20T03:55:06ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/29393702939370SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis)Chang He0Cheng-Rong Yu1Mary J. Mattapallil2Lin Sun3Joseph Larkin III4Charles E. Egwuagu5Molecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USAImmunoregulation Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USADepartment of Microbiology & Cell Science, University of Florida, Gainesville, FL 32611, USAMolecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USAUveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation of pathogenic Th1 and Th17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR) that inhibits JAK2/STAT1 pathways has recently been shown to suppress experimental autoimmune uveitis (EAU). However, it is not clear whether SOCS1-KIR ameliorated uveitis by targeting JAK/STAT pathways of pathogenic lymphocytes or via inhibition of macrophages and antigen-presenting cells that also enter the retina during EAU. To further investigate mechanisms that mediate SOCS1-KIR effects and evaluate the efficacy of SOCS1-KIR as an investigational drug for chronic uveitis, we induced EAU in rats by adoptive transfer of uveitogenic T-cells and monitored disease progression and severity by slit-lamp microscopy, histology, and optical coherence tomography. Topical administration of SOCS1-KIR ameliorated acute and chronic posterior uveitis by inhibiting Th17 cells and the recruitment of inflammatory cells into retina while promoting expansion of IL-10-producing Tregs. We further show that SOCS1-KIR conferred protection of resident retinal cells that play critical role in vision from cytotoxic effects of inflammatory cytokines by downregulating proapoptotic genes. Thus, SOCS1-KIR suppresses uveitis and confers neuroprotective effects and might be exploited as a noninvasive treatment for chronic uveitis.http://dx.doi.org/10.1155/2016/2939370 |
| spellingShingle | Chang He Cheng-Rong Yu Mary J. Mattapallil Lin Sun Joseph Larkin III Charles E. Egwuagu SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis) Mediators of Inflammation |
| title | SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis) |
| title_full | SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis) |
| title_fullStr | SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis) |
| title_full_unstemmed | SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis) |
| title_short | SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis) |
| title_sort | socs1 mimetic peptide suppresses chronic intraocular inflammatory disease uveitis |
| url | http://dx.doi.org/10.1155/2016/2939370 |
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