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J. Yamada, J. Hamuro, K. Terai, C. Mochida, K. Endo, T. Ooteki, S. Kinoshita; IL-15 Plays an Important Role in the Induction of Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2835.
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© ARVO (1962-2015); The Authors (2016-present)
Experimental autoimmune uveoretinitis (EAU) is believed to be a Th1-mediated autoimmune disease. However, endogenous IFN-γ negatively regulates EAU, which suggests the presence of other immune mechanisms to develop EAU. IL-15 is known to induce IFN-γ secretion by NK cells, IL-12 secretion by dendritic cells, as well as the induction of the TH17 response. The present study was designed to determine the role of IL-15 in a murine model of EAU.
Wild-type C57BL/6 or IL-15-knockout (KO) mice (C57BL/6 background) were immunized with human IRBP peptide 1-20 (hIRBP-p). Severity of EAU was assessed clinically and histopathologically 21 days after IRBP immunization. RNA was isolated from the cervical lymph nodes of either normal or EAU mice. IL-12p40, IL-15, Il-17a, IL-17f, IL-18, IL-23a, IL-27, and IFN-γ mRNA levels were analyzed by Real-Time PCR.
Normal, EAU-free IL-15KO mice showed a 6- to 10-fold reduction of the gene expression levels of IFN-γ, IL-12, IL-17a, and IL-17f compared with disease-free wild-type mice. Accordingly, IL-15KO mice showed the reduced EAU induction both clinically and histopathologically. In the histopathological comparison, IL-15KO mice (n = 10) developed significantly lower levels of EAU (1.6 ±; 1.0) compared to wild-type mice (n = 10) (2.9 ±; 0.7, p < 0.0003). In the lymph nodes of C57BL/6 mice with EAU, only IFN-γ mRNA up-regulation was detected significantly in comparison with EAU-free C57BL/6 mice.
IL-15 plays an important role in EAU development. Recent reports reveal that IL-17 is known to play a critical role in the induction of experimental autoimmune encephalomyelitis (EAE). The suppressed EAU development observed in IL-15KO mice may be due to the suppression of both the Th1 and Th17 responses. We are now conducting a study to investigate the spatial and temporal regulation of mRNA expression and cytokine production in eye tissues.
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