TNFα suppresses IFNγ‐induced MHC Class II expression in retinal pigmented epithelial cells by down regulating Class II trans‐activator mRNA

Abstract

Abstract Purpose The expression of MHC class II molecules induced by IFNγ on RPE cells plays a crucial role in the development of autoimmune uveitis. As TNFα is commonly coexpressed with IFNγ in this disease, we have investigated the effects of TNFα on the IFNγ mediated MHC II induction in RPE cells. Methods ARPE‐19 were cultured and stimulated with TNFα, IFNγ, IL‐1β and different combination of these cytokines. After cytokine treatment, we have analysed the expression of MHCII and ICAM‐1 by flow cytometry. IDO induction was studied by Western blotting. The activation and expression of two proteins involved in IFN pathway: IRF1 and STAT was analysed by Western blot. We have also monitored the effects of TNFα and IFNγ on the expression of CIITA by quantitative RT‐PCR. Results TNFα, but not IL‐1, inhibits IFNγ induced MHC class II expression on the surface of ARPE cells. We did not observed an inhibitory effect of TNFα on the expression of ICAM and IDO induced by IFNγ. Similarly, STAT1 phosphorylation and IRF1 induction obtained after IFNγ treatment were not affected by TNFα. On the contrary, we found that TNFα suppresses IFNγ induced CIITA mRNA accumulation. Conclusion TNFα suppresses IFNγ induced CIITA mRNA accumulation and MHC II expression in human retinal pigment cells.