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Key role for IL-21 in experimental autoimmune uveitis
Lu Wang, Cheng-Rong Yu, Hyoung-Pyo Kim, Wei Liao, William G. Telford, Charles E. Egwuagu and Warren J. Leonard
Proceedings of the National Academy of Sciences of the United States of America
Vol. 108, No. 23 (June 7, 2011), pp. 9542-9547
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/25831266
Page Count: 6
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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.
Proceedings of the National Academy of Sciences of the United States of America © 2011 National Academy of Sciences