Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9542-7. doi: 10.1073/pnas.1018182108. Epub 2011 May 18.
IL-21 is a pleiotropic type 1 cytokine that shares the common cytokine receptor γ-chain, γ(c), with IL-2, IL-4, IL-7, IL-9, and IL-15. IL-21 is most homologous to IL-2. These cytokines are encoded by adjacent genes, but they are functionally distinct. Whereas IL-2 promotes development of regulatory T cells and confers protection from autoimmune disease, IL-21 promotes differentiation of Th17 cells and is implicated in several autoimmune diseases, including type 1 diabetes and systemic lupus erythematosus. However, the roles of IL-21 and IL-2 in CNS autoimmune diseases such as multiple sclerosis and uveitis have been controversial. Here, we generated Il21-mCherry/Il2-emGFP dual-reporter transgenic mice and showed that development of experimental autoimmune uveitis (EAU) correlated with the presence of T cells coexpressing IL-21 and IL-2 into the retina. Furthermore, Il21r(-/-) mice were more resistant to EAU development than wild-type mice, and adoptive transfer of Il21r(-/-) T cells induced much less severe EAU, underscoring the need for IL-21 in the development of this disease and suggesting that blocking IL-21/γ(c)-signaling pathways may provide a means for controlling CNS auto-inflammatory diseases.
白细胞介素 21（IL-21）是一种具有多效性的 I 型细胞因子，与白细胞介素 2（IL-2）、IL-4、IL-7、IL-9 和 IL-15 共享共同的细胞因子受体 γ 链（γ（c））。IL-21 与 IL-2 最为同源。这些细胞因子由相邻的基因编码，但它们具有不同的功能。IL-2 促进调节性 T 细胞的发育，并赋予其免受自身免疫性疾病的保护，而 IL-21 则促进 Th17 细胞的分化，并与几种自身免疫性疾病有关，包括 1 型糖尿病和系统性红斑狼疮。然而，IL-21 和 IL-2 在多发性硬化症和葡萄膜炎等中枢神经系统自身免疫性疾病中的作用一直存在争议。在这里，我们生成了 Il21-mCherry/Il2-emGFP 双报告转基因小鼠，并表明实验性自身免疫性葡萄膜炎（EAU）的发展与视网膜中同时表达 IL-21 和 IL-2 的 T 细胞的存在有关。此外，与野生型小鼠相比，Il21r（-/-）小鼠对 EAU 的发展更具抗性，并且 Il21r（-/-）T 细胞的过继转移引起的 EAU 要轻得多，这突出表明在这种疾病的发展中需要 IL-21，并表明阻断 IL-21/γ（c）-信号通路可能为控制中枢神经系统自身炎症性疾病提供一种手段。
