Abstract
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.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmune Diseases / genetics
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Autoimmune Diseases / immunology*
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Autoimmune Diseases / metabolism
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cell Proliferation
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Cells, Cultured
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Flow Cytometry
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Interleukin-10 / immunology
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Interleukin-10 / metabolism
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Interleukin-17 / immunology
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Interleukin-17 / metabolism
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Interleukin-1beta / immunology
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Interleukin-1beta / metabolism
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Interleukin-2 / genetics
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Interleukin-2 / immunology*
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Interleukin-2 / metabolism
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Interleukin-6 / immunology
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Interleukin-6 / metabolism
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Interleukins / genetics
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Interleukins / immunology*
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Interleukins / metabolism
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Receptors, Interleukin-21 / genetics
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Receptors, Interleukin-21 / immunology
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Receptors, Interleukin-21 / metabolism
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Retina / metabolism
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Retina / pathology
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Uveitis / genetics
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Uveitis / immunology*
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Uveitis / metabolism
Substances
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Interleukin-17
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Interleukin-1beta
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Interleukin-2
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Interleukin-6
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Interleukins
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Luminescent Proteins
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Receptors, Interleukin-21
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Interleukin-10
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interleukin-21