期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2011
卷号：108
期号：23
页码：9542-9547
DOI：10.1073/pnas.1018182108
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：IL-21 is a pleiotropic type 1 cytokine that shares the common cytokine receptor {gamma}-chain, {gamma}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/{gamma}c-signaling pathways may provide a means for controlling CNS auto-inflammatory diseases.
