WSX-1 plays a significant role for the initiation of experimental autoimmune uveitis

Abstract

WSX-1 is a subunit of the IL-27R, which plays a critical role in the initiation of Th 1 responses. Murine experimental autoimmune uveitis (EAU) is a model of human autoimmune uveitis, in which a Th 1 response predominates in the pathogenetic process. To explore the role of WSX-1 in this model, WSX-1-1- mice were immunized with interphotoreceptor retinoid-binding protein peptide 1-20 to induce EAU. We found that the EAU clinical and histological scores were lower in the WSX-1-1- mice up to day 21, whereas after day 21, the EAU scores were the same between the wild-type (WT) and WSX-1-1- mice with both declining at the same rate. In contrast to T lymphocytes from WT mice, WSX-1-1- T lymphocytes on day 9 after immunization failed to produce IFN-γ. Similarly, expression of Th 1-related chemokines, such as regulated on activation, normal T cell expressed and secreted and IP-10, in the eye was reduced in WSX-1-1- mice compared with WT mice on day 13 after immunization. In addition, sub-retinal transfer of lymphocytes from WSX-1-1- mice on day 9 after immunization did not induce EAU in the recipient mice. Importantly, IFN-γ production, chemokine expression and the transferability of disease by lymphocytes became comparable for WSX-1-1- and WT mice at later stages. Thus, IL-27/WSX-1 affects the early development of EAU, and might be a target for therapy during the onset of autoimmune uveitis in humans. © 2007 Oxford University Press.