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.
Pubmed ID: 21593413 RIS Download
Animals | Autoimmune Diseases | CD4-Positive T-Lymphocytes | Cell Proliferation | Cells, Cultured | Flow Cytometry | Interleukin-10 | Interleukin-17 | Interleukin-1beta | Interleukin-2 | Interleukin-6 | Interleukins | Luminescent Proteins | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Receptors, Interleukin-21 | Retina | Reverse Transcriptase Polymerase Chain Reaction | T-Lymphocytes | Uveitis