| First Author | Ke Y | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 5 | Pages | 2130-9 |
| PubMed ID | 21795593 | Mgi Jnum | J:179139 |
| Mgi Id | MGI:5301196 | Doi | 10.4049/jimmunol.1100482 |
| Citation | Ke Y, et al. (2011) IL-22-induced regulatory CD11b+ APCs suppress experimental autoimmune uveitis. J Immunol 187(5):2130-9 |
| abstractText | 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-gamma(+) 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-beta. 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. |
