کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8795009 1602801 2018 47 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The immunopathogenesis of chronic and relapsing autoimmune uveitis - Lessons from experimental rat models
ترجمه فارسی عنوان
ایمونوپاتوژنز یووئیت اتوایمیون مزمن و عودکننده - درسهایی از مدلهای موشهای آزمایشگاهی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی سیستم های حسی
چکیده انگلیسی
Autoimmune diseases usually follow a relapsing-remitting or a chronic progressive course. To understand the underlying immunopathogenesis we investigated experimental Lewis rat models displaying both disease types, which were only dependent on the autoantigen peptide used for immunization. Retinal S-Antigen-peptide PDSAg induces chronic, monophasic disease, whilst interphotoreceptor retinoid-binding protein (IRBP)-peptide R14 causes a spontaneously relapsing-remitting course. R14-mediated uveitis can be re-induced by immunization; PDSAg-induced disease is even preventable by prior CFA-injection. T cells with different antigen specificities preferentially infiltrate the eyes from different sites, e.g. choroid or retinal vessels, they remain in the retina after resolution of inflammation for many weeks. The major inflammatory cell populations in the eyes during rat uveitis are CD4+ or CD8+ monocytes/macrophages. Chemokine mutants only suppress PDSAg-mediated EAU, while IFN-α-treatment ameliorated R14-, but worsened PDSAg-induced disease. Comparison of T cells revealed upregulated expression of 26 genes related to various signal transduction pathways upstream and downstream of IFN-γ only in T cells causing relapsing EAU. Intraocular injection of IFN-γ induces synchronized relapses in R14-mediated uveitis, while VEGF-expression of PDSAg-specific T cells causing chronic disease induced chorioretinal neovascularization that is suppressed by anti-CD146 antibody. Intraocular T cells from rat eyes during EAU express IL-17, IFN-γ or IL-10, with dynamic changes of the cell populations during the disease course, differing in both disease types. Immunization of animals with a mixture of both antigens suppressed relapses, indicating a dominance of the monophasic disease. Understanding the exact pathogenesis of both disease courses is key to developing novel therapies for autoimmune diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Progress in Retinal and Eye Research - Volume 65, July 2018, Pages 107-126
نویسندگان
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