Key role for IL-21 in experimental autoimmune uveitis
Copyright policy )Key role for IL-21 in experimental autoimmune uveitis
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.
- National Cancer Institute United States
- National Institutes of Health United States
- National Institute of Health Pakistan
- Yonsei University Medical Library Korea (Republic of)
- National Eye Institute United States
CD4-Positive T-Lymphocytes, Interleukin-6/metabolism, Interleukin-1beta, Interleukin-21/metabolism, Inbred C57BL, Transgenic, Mice, Interleukins/genetics, Interleukins/metabolism, Receptors, Cells, Cultured, Mice, Knockout, Retina/metabolism, Cultured, Interleukin-2/immunology*, Reverse Transcriptase Polymerase Chain Reaction, Retina/pathology, Interleukin-17, T-Lymphocytes/metabolism, Flow Cytometry, Interleukin-10, CD4-Positive T-Lymphocytes/immunology, Receptors, Interleukin-21, Luminescent Proteins/genetics, Interleukin-1beta/immunology, Interleukin-2/genetics, Interleukin-2/metabolism, Cells, Knockout, Interleukin-21/immunology, 610, Mice, Transgenic, Uveitis/immunology*, Retina, Autoimmune Diseases, Interleukin-10/metabolism, Uveitis/genetics, Autoimmune Diseases/genetics, Interleukins/immunology*, 616, Animals, Cell Proliferation, CD4-Positive T-Lymphocytes/metabolism, Interleukin-6, Interleukins, Autoimmune Diseases/metabolism, T-Lymphocytes/immunology, Interleukin-21/genetics, Interleukin-17/immunology, Luminescent Proteins/metabolism, Autoimmune Diseases/immunology*, Mice, Inbred C57BL, Luminescent Proteins, Interleukin-17/metabolism, Uveitis/metabolism, Interleukin-1beta/metabolism, Interleukin-2, Interleukin-6/immunology, Interleukin-10/immunology
CD4-Positive T-Lymphocytes, Interleukin-6/metabolism, Interleukin-1beta, Interleukin-21/metabolism, Inbred C57BL, Transgenic, Mice, Interleukins/genetics, Interleukins/metabolism, Receptors, Cells, Cultured, Mice, Knockout, Retina/metabolism, Cultured, Interleukin-2/immunology*, Reverse Transcriptase Polymerase Chain Reaction, Retina/pathology, Interleukin-17, T-Lymphocytes/metabolism, Flow Cytometry, Interleukin-10, CD4-Positive T-Lymphocytes/immunology, Receptors, Interleukin-21, Luminescent Proteins/genetics, Interleukin-1beta/immunology, Interleukin-2/genetics, Interleukin-2/metabolism, Cells, Knockout, Interleukin-21/immunology, 610, Mice, Transgenic, Uveitis/immunology*, Retina, Autoimmune Diseases, Interleukin-10/metabolism, Uveitis/genetics, Autoimmune Diseases/genetics, Interleukins/immunology*, 616, Animals, Cell Proliferation, CD4-Positive T-Lymphocytes/metabolism, Interleukin-6, Interleukins, Autoimmune Diseases/metabolism, T-Lymphocytes/immunology, Interleukin-21/genetics, Interleukin-17/immunology, Luminescent Proteins/metabolism, Autoimmune Diseases/immunology*, Mice, Inbred C57BL, Luminescent Proteins, Interleukin-17/metabolism, Uveitis/metabolism, Interleukin-1beta/metabolism, Interleukin-2, Interleukin-6/immunology, Interleukin-10/immunology
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