title: IL-22-induced regulatory CD11b+ APCs suppress experimental autoimmune uveitis.
abstract: We have previously reported that IL-17(+) interphotoreceptor retinoid-binding protein (IRBP) 161-180-specific T cells have a strong pathogenic effect in experimental autoimmune uveitis (EAU) induced in B10RIII mice; however, this pathogenic activity is not solely attributable to the major cytokine, IL-17, produced by these cells. To determine whether other cytokines produced by Th17 cells show a stronger association with their pathogenic activity, we studied the role of IL-22 in EAU. IL-22 is one of the major cytokines produced by these cells. Our results showed that administration of small doses of IL-22 to EAU-susceptible mice significantly reduced the severity of EAU. In addition, mice treated with IL-22 generated decreased numbers of IFN-γ(+) and IL-17(+) uveitogenic T cells, but increased numbers of Foxp3(+) regulatory T cells. Mechanistic studies showed that the effect of the injected IL-22 was on CD11b(+) APCs, which expressed increased levels of IL-22R during induction of disease following immunization with uveitogenic Ag. In vitro IL-22 treatment of CD11b(+) APCs collected from Ag-primed mice resulted in increased expression of programmed death ligand-1 and the production of increased amounts of IL-10 and TGF-β. Moreover, IL-22-treated CD11b(+) APCs caused IRBP161-180-specific T cells to lose their uveitogenic activity and acquire immunosuppressive activity, which suppressed the induction of EAU by additional pathogenic IRBP161-180-specific effector T cells.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ke
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
authors.forename: Guomin
authors.initials: G
authors.lastname: Jiang
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D039481:CD11b Antigen; D007378:Interleukins; D000097043:Interleukin-22