title: Cutting Edge: IL-1 Receptor Signaling is Critical for the Development of Autoimmune Uveitis.
abstract: IL-1β is a proinflammatory cytokine important for local and systemic immunity. However, aberrant production of this cytokine is implicated in pathogenic mechanisms of a number of inflammatory diseases, including Behçet's disease and age-related macular degeneration. In this study, we report the increased secretion of IL-1β in the retina by neutrophils, macrophages, and dendritic cells during ocular inflammation and show that loss of IL-1R signaling confers protection from experimental autoimmune uveitis. Moreover, the amelioration of experimental autoimmune uveitis in Il1r-deficient mice was associated with reduced infiltration of inflammatory cells into the retina and decreased numbers of uveitogenic Th17 cells that mediate uveitis. These findings indicate the possible utility of IL-1R-blocking agents for the treatment of ocular inflammatory diseases.
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Chi-Keung
authors.initials: CK
authors.lastname: Wan
authors.affiliation: Molecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Chang
authors.identifier: http://orcid.org/0000-0003-1178-5950
authors.initials: C
authors.lastname: He
authors.affiliation: Molecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Molecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892 wjl@helix.nih.gov egwuaguc@nei.nih.gov.
authors.forename: Charles E
authors.identifier: http://orcid.org/0000-0002-9986-3839
authors.initials: CE
authors.lastname: Egwuagu
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and wjl@helix.nih.gov egwuaguc@nei.nih.gov.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D053583:Interleukin-1beta / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014605:Uveitis / Q000276:immunology*
chemical_list: D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1