A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis

• Published in: PloS one 2020-02, Vol.15 (2), p.e0227524-e0227524
• Main Authors: Ahmed, Chulbul M, Ildefonso, Cristhian J, Johnson, Howard M, Lewin, Alfred S
• Format: Article
• Language: English
• Subjects: Administration, Oral; Analysis; Animals; Anti-inflammatory agents; Antigens; Autoimmune Diseases - drug therapy; Autoimmune Diseases - pathology; Autoimmune Diseases - physiopathology; Biological response modifiers; Biology and Life Sciences; C-Terminus; Cell differentiation; Cell Line; Cell proliferation; Cell Proliferation - drug effects; Chemokines; Cytokines; Disease; Disease Models, Animal; Diseases; Disruption; Drug development; Electric Impedance; Electroretinograms; Electroretinography; Experimental autoimmune uveitis; Experimental autoimmune uveoretinitis; Eye Proteins - metabolism; Gene expression; Histology; Humans; Immunization; Inflammation; Inflammation Mediators - metabolism; Interferon; Interferon alpha; Interferon Type I - chemistry; Interleukin-17 - metabolism; Interphotoreceptor retinoid-binding protein; Lymphocytes; Lymphocytes T; Lysine; Medicine and Health Sciences; Mice; Multiple sclerosis; NF-kappa B - metabolism; NF-κB protein; Peptides; Peptides - therapeutic use; Protein binding; Proteins; Research and Analysis Methods; Retina; Retina - drug effects; Retina - pathology; Retina - physiopathology; Retinol-Binding Proteins - metabolism; Rodents; Signal Transduction - drug effects; Spleen - drug effects; Spleen - pathology; Splenocytes; Structure-function relationships; T cell receptors; T cells; Therapeutics; Tight Junctions - drug effects; Tight Junctions - metabolism; Tumor necrosis factor; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α; Uveitis; Uveitis - drug therapy; Uveitis - pathology; Uveitis - physiopathology; α-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0227524

Experimental autoimmune uveitis (EAU) in rodents recapitulates many features of the disease in humans and has served as a useful tool for the development of therapeutics. A peptide from C-terminus of interferon α1, conjugated to palmitoyl-lysine for cell penetration, denoted as IFNα-C, was tested for its anti-inflammatory properties in ARPE-19 cells, followed by testing in a mouse model of EAU. Treatment with IFNα-C and evaluation by RT-qPCR showed the induction of anti-inflammatory cytokines and chemokine. Inflammatory markers induced by treatment with TNFα were suppressed when IFNα-C was simultaneously present. TNF-α mediated induction of NF-κB and signaling by IL-17A were attenuated by IFNα-C. Differentiated ARPE-19 cells were treated with TNFα in the presence or absence IFNα-C and analyzed by immmunhistochemistry. IFNα-C protected against the disruption integrity of tight junction proteins. Similarly, loss of transepithelial resistance caused by TNFα was prevented by IFNα-C. B10.RIII mice were immunized with a peptide from interphotoreceptor binding protein (IRBP) and treated by gavage with IFNα-C. Development of uveitis was monitored by histology, fundoscopy, SD-OCT, and ERG. Treatment with IFNα-C prevented uveitis in mice immunized with the IRBP peptide. Splenocytes isolated from mice with ongoing EAU exhibited antigen-specific T cell proliferation that was inhibited in the presence of IFNα-C. IFNα-C peptide exhibits anti-inflammatory properties and protects mice against damage to retinal structure and function suggesting that it has therapeutic potential for the treatment of autoimmune uveitis.