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The immunopathogenesis of chronic and relapsing autoimmune uveitis - Lessons from experimental rat models
- Source :
- Progress in retinal and eye research. 65
- Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Chemokine
T-Lymphocytes
Inflammation
Autoimmune Diseases
Neovascularization
Pathogenesis
Uveitis
03 medical and health sciences
0302 clinical medicine
Antigen
Recurrence
medicine
Animals
biology
Neovascularization, Pathologic
business.industry
medicine.disease
eye diseases
Sensory Systems
Rats
Ophthalmology
Disease Models, Animal
030104 developmental biology
Immunology
Chronic Disease
biology.protein
Cytokines
sense organs
Antibody
medicine.symptom
business
CD8
030215 immunology
Subjects
Details
- ISSN :
- 18731635
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Progress in retinal and eye research
- Accession number :
- edsair.doi.dedup.....e23d336fe85898518a52353e0b61823c