TY - JOUR
T1 - Regulatory Effects of IFN-beta on the Development of Experimental Autoimmune Uveoretinitis in B10RIII Mice
AU - Sun, Min
AU - Yang, Yan
AU - Yang, Peizeng
AU - Lei, Bo
AU - Du, Liping
AU - Kijlstra, Aize
PY - 2011/5/6
Y1 - 2011/5/6
N2 - Background: Experimental autoimmune uveoretinitis (EAU) serves as a model for human intraocular inflammation. IFN-beta has been used in the treatment of certain autoimmune diseases. Earlier studies showed that it ameliorated EAU; however, the mechanisms involved in this inhibition are still largely unknown. Methodology/Principal Findings: B10RIII mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 161-180 in Complete Freund's adjuvant. Splenocytes from different time points after immunization were used to evaluate the expression of IFN-beta. An increased expression of IFN-beta was observed during EAU and its highest expression was observed on day 16, 3 days after the peak of intraocular inflammation. Splenocytes and draining lymph node cells from mice immunized with IRBP(161-180) on day 13 and control mice were activated with anti-CD3/anti-CD28 antibodies or IRBP(161-180) to evaluate the production of IFN-gamma and IL-17. The results showed that IFN-gamma and IL-17 were significantly higher in immunized mice as compared to the control mice when exposed to anti-CD3/anti-CD28 antibodies. However, the production of IFN-gamma and IL-17 was detected only in immunized mice, but not in the control mice when stimulated with IRBP(161-180). Multiple subcutaneous injections of IFN-beta significantly inhibited EAU activity in association with a down-regulated expression of IFN-gamma, IL-17 and an enhanced IL-10 production. In an in vitro system using cells from mice, IFN-beta suppressed IFN-gamma production by CD4(+)CD62L(-) T cells, IL-17 production by CD4(+)CD62L(+/-) T cells and proliferation of CD4(+)CD62L(+/-) T cells. IFN-beta inhibited the secretion of IL-6, but promoted the secretion of IL-10 by monocytes. IFN-beta-treated monocytes inhibited IL-17 secretion by CD4(+)CD62L(+/-) T cells, but did not influence IFN-gamma expression and T cell proliferation. Conclusions/Significance: IFN-beta may exert its inhibitory effect on EAU by inhibiting Th1, Th17 cells and modulating relevant cytokines. IFN-beta may provide a potential treatment for diseases mediated by Th1 and Th17 cells.
AB - Background: Experimental autoimmune uveoretinitis (EAU) serves as a model for human intraocular inflammation. IFN-beta has been used in the treatment of certain autoimmune diseases. Earlier studies showed that it ameliorated EAU; however, the mechanisms involved in this inhibition are still largely unknown. Methodology/Principal Findings: B10RIII mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 161-180 in Complete Freund's adjuvant. Splenocytes from different time points after immunization were used to evaluate the expression of IFN-beta. An increased expression of IFN-beta was observed during EAU and its highest expression was observed on day 16, 3 days after the peak of intraocular inflammation. Splenocytes and draining lymph node cells from mice immunized with IRBP(161-180) on day 13 and control mice were activated with anti-CD3/anti-CD28 antibodies or IRBP(161-180) to evaluate the production of IFN-gamma and IL-17. The results showed that IFN-gamma and IL-17 were significantly higher in immunized mice as compared to the control mice when exposed to anti-CD3/anti-CD28 antibodies. However, the production of IFN-gamma and IL-17 was detected only in immunized mice, but not in the control mice when stimulated with IRBP(161-180). Multiple subcutaneous injections of IFN-beta significantly inhibited EAU activity in association with a down-regulated expression of IFN-gamma, IL-17 and an enhanced IL-10 production. In an in vitro system using cells from mice, IFN-beta suppressed IFN-gamma production by CD4(+)CD62L(-) T cells, IL-17 production by CD4(+)CD62L(+/-) T cells and proliferation of CD4(+)CD62L(+/-) T cells. IFN-beta inhibited the secretion of IL-6, but promoted the secretion of IL-10 by monocytes. IFN-beta-treated monocytes inhibited IL-17 secretion by CD4(+)CD62L(+/-) T cells, but did not influence IFN-gamma expression and T cell proliferation. Conclusions/Significance: IFN-beta may exert its inhibitory effect on EAU by inhibiting Th1, Th17 cells and modulating relevant cytokines. IFN-beta may provide a potential treatment for diseases mediated by Th1 and Th17 cells.
U2 - 10.1371/journal.pone.0019870
DO - 10.1371/journal.pone.0019870
M3 - Article
C2 - 21573074
SN - 1932-6203
VL - 6
SP - 10
JO - PLOS ONE
JF - PLOS ONE
IS - 5
ER -