IFN-beta Inhibits the Increased Expression of IL-9 during Experimental Autoimmune Uveoretinitis

Purpose: It has been shown that IL-9 plays a proinflammatory role in the pathogenesis of certain autoimmune diseases. This study was designed to investigate the possible role of IL-9 in the development of experimental autoimmune uveoretinitis (EAU) and the effect of IFN-beta on its expression. Methods: EAU was induced in B10RIII mice by immunization with interphotoreceptor retinoid-binding protein peptide 161-180 (IRBP161-180). IFN-beta was administered subcutaneously to IRBP161-180 immunized mice every other day from day one before immunization to the end of the study. Splenocytes and draining lymph node (DLN) cells from EAU mice or control mice or EAU mice treated with IFN-beta or PBS were stimulated with anti-CD3/CD28 or IRBP161-180 for 3 days. Naive T cells cultured under Th1 or Th17 polarizing conditions were incubated in the presence or absence of IFN-beta for 4 days. Effector/memory T cells were activated by anti-CD3/CD28 in the presence or absence of IFN-beta for 3 days. IFN-beta-treated monocytes were cocultured with naive T cells or effector/memory T cells for 3 days. Culture supernatants were collected and IL-9 was detected by ELISA. Results: IL-9 expression in splenocytes and DLN cells was increased in EAU mice during the inflammatory phase and returned back to lower levels during the recovery phase. IFN-beta in vivo treatment significantly inhibited EAU activity in association with a down-regulated expression of IL-9. In vitro polarized Th1 and Th17 cells both secreted IL-9 and the addition of IFN-beta suppressed production of IL-9 by both Th subsets. Beside its effect on polarized Th cells, IFN-beta also suppressed the secretion of IL-9 by effector/memory T cells. However, IFN-beta-treated monocytes had no effect on the production of IL-9 when cocultured with naive or effector/memory T cells. Conclusion: IL-9 expression is increased during EAU which could be suppressed by IFN-b.