WSX-1 plays a significant role for the initiation of experimental autoimmune uveitis.
WSX-1 is a subunit of the IL-27R, which plays a critical role in the initiation of T(h)1 responses. Murine experimental autoimmune uveitis (EAU) is a model of human autoimmune uveitis, in which a T(h)1 response predominates in the pathogenetic process. To explore the role of WSX-1 in this model, WSX-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(-/-) mice up to day 21, whereas after day 21, the EAU scores were the same between the wild-type (WT) and WSX-1(-/-) mice with both declining at the same rate. In contrast to T lymphocytes from WT mice, WSX-1(-/-) T lymphocytes on day 9 after immunization failed to produce IFN-gamma. Similarly, expression of T(h)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(-/-) mice compared with WT mice on day 13 after immunization. In addition, sub-retinal transfer of lymphocytes from WSX-1(-/-) mice on day 9 after immunization did not induce EAU in the recipient mice. Importantly, IFN-gamma production, chemokine expression and the transferability of disease by lymphocytes became comparable for WSX-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.
Sonoda
Koh-Hei
KH
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. sonodak@med.kyushu-u.ac.jp
Yoshimura
Takeru
T
Takeda
Atsunobu
A
Ishibashi
Tatsuro
T
Hamano
Shinjiro
S
Yoshida
Hiroki
H
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology*; D018123:Receptors, Interleukin; D018417:Th1 Cells / Q000276:immunology; D014605:Uveitis / Q000276:immunology*
C484747:Il27ra protein, mouse; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D007371:Interferon-gamma