WSX-1 plays a significant role for the initiation of experimental autoimmune uveitis.
WSX-1 plays a significant role for the initiation of experimental autoimmune uveitis.
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DOI：
10.1093/intimm/dxl125
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发表时间：
2006-11
影响因子：
4.4
通讯作者：
K. Sonoda;T. Yoshimura;A. Takeda;T. Ishibashi;S. Hamano;H. Yoshida
中科院分区：
文献类型：
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作者：
K. Sonoda;T. Yoshimura;A. Takeda;T. Ishibashi;S. Hamano;H. Yoshida
WSX-1是IL-27 R的一个亚基，在T（h）1应答的启动中起关键作用。小鼠实验性自身免疫性葡萄膜炎（EAU）是人类自身免疫性葡萄膜炎的模型，其中T（h）1反应在发病过程中占主导地位。为了探讨WSX-1在该模型中的作用，用感光细胞间维甲酸结合蛋白肽1-20免疫WSX-1（-/-）小鼠以诱导EAU。我们发现WSX-1（-/-）小鼠的EAU临床和组织学评分在第21天之前较低，而在第21天之后，野生型（WT）和WSX-1（-/-）小鼠之间的EAU评分相同，两者以相同的速率下降。与WT小鼠的T淋巴细胞相反，免疫后第9天的WSX-1（-/-）T淋巴细胞不能产生IFN-γ。同样，与WT小鼠相比，免疫后第13天，WSX-1（-/-）小鼠眼中T（h）1相关趋化因子（例如活化调节因子、正常T细胞表达和分泌因子以及IP-10）的表达减少。此外，在免疫后第9天从WSX-1（-/-）小鼠视网膜下转移淋巴细胞不会在受体小鼠中诱导EAU。重要的是，IFN-γ的产生、趋化因子的表达和淋巴细胞对疾病的转移性在WSX-1（-/-）和WT小鼠的后期阶段变得相当。因此，IL-27/WSX-1影响EAU的早期发展，并且可能是人类自身免疫性葡萄膜炎发作期间的治疗靶点。
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.