Therapeutic targeting of STAT3 (signal transducers and activators of transcription 3) pathway inhibits experimental autoimmune uveitis

• Published in: PloS one Vol. 7; no. 1; p. e29742
• Main Authors: Yu, Cheng-Rong, Lee, Yun Sang, Mahdi, Rashid M, Surendran, Narayanan, Egwuagu, Charles E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.01.2012; Public Library of Science (PLoS)
• Subjects: Analysis; Animal tissues; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Autoimmune diseases; Autoimmune Diseases - complications; Autoimmune Diseases - drug therapy; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmunity; Biology; Biopsy; Blood & organ donations; Blood-brain barrier; Brain research; CCR6 protein; CD4 antigen; Cells, Cultured; Central nervous system; Chemotaxis; Clonal deletion; CXCR3 protein; Cytokines; Dendritic cells; Disease; Disease Models, Animal; Drug development; Drug Evaluation, Preclinical; Electronic components; Experimental allergic encephalomyelitis; Experimental autoimmune uveitis; Experimental autoimmune uveoretinitis; Gene deletion; Health aspects; Helper cells; Human subjects; Humans; Immunology; Inflammatory diseases; Laboratory animals; Ligands; Lymphocytes; Lymphocytes T; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Targeted Therapy; Multiple sclerosis; Nervous system; Proteins; Recruitment; Retina; Retina - drug effects; Retina - immunology; Retina - metabolism; Retina - pathology; Rodents; Signal Transduction - drug effects; Signal Transduction - genetics; Signal Transduction - immunology; Signal Transduction - physiology; Stat3 protein; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - physiology; T cells; Th17 Cells - drug effects; Th17 Cells - metabolism; Th17 Cells - physiology; Therapeutic targets; Transcription (Genetics); Transcription factors; Transducers; Uveitis; Uveitis - complications; Uveitis - drug therapy; Uveitis - genetics; Uveitis - immunology; United States > US; Maryland; India

Mice with targeted deletion of STAT3 in CD4(+) T-cells do not develop experimental autoimmune uveitis (EAU) or experimental autoimmune encephalomyelitis (EAE), in part, because they cannot generate pathogenic Th17 cells. In this study, we have used ORLL-NIH001, a small synthetic compound that inhibi...