Coordinated gene expression of Th17- and Treg-associated molecules correlated with resolution of the monophasic experimental autoimmune uveitis

PURPOSE To investigate the role of T-cell-mediated immune response in a monophasic experimental autoimmune uveitis (EAU). METHODS A monophasic EAU was induced in Lewis rats by immunization with interphotoreceptor retinoid-binding protein peptide. Optimized quantitative real-time RT-PCR was used for consecutive measurement of the relative expression of Th17-associated molecules, including interleukin 6 (IL-6), transforming growth factor-β (TGF-β), interleukin 23p19 (IL-23p19), interleukin 23p40 (IL-23p40), CD4, CD8, major histocompatibility complex I (MHC I), major histocompatibility complex II (MHC II), interleukin 17 (IL-17), interleukin 17F (IL-17F), interleukin 17 receptor A (IL-17RA), retinoic acid-related orphan receptor γt (RORγt) and Chemokine receptor 6 (CCR6), in addition to Treg-related forkhead box P3 (Foxp3), C-X-C chemokine receptor type 5 (CXCR5), and cluster of differentiation 25 (CD25) at the initiation, effector, and resolution phases of EAU and compared with those at 14 days post-immunization of control animals. Immunohistochemisty was used to examine IL-17 expression in retinas. Glial fibrillary acidic protein retinal astrocytes, Neuronal class III β-Tubulin(Tuj1(+))retinal ganglion cells, and infiltrating CD11b(+) microglia were analyzed by fluorescent microscopy in a kinetic manner. RESULTS Our results indicated well organized T-cell activity, measured by relative expression of multiple T-cell-related factors at the mRNA level, synchronized with the initiation of autoimmune inflammation, and thereafter resolution of the monophasic EAU. Immune balance was achieved several times through coordinated expression of Th17- and Treg-related factors. The expression pattern of these factors and results from immunochemistry with an IL-17 antibody indicated that there may be intensive crosstalk between infiltrating immune cells and the resident neural cells, which were significantly activated during the course of disease. CONCLUSIONS T-cell-mediated immune response played a positive role in resolution of the monophasic EAU.