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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

Authors

  • Wang L
  • Yu CR
  • Kim HP
  • Liao W
  • Telford WG
  • Egwuagu CE
  • Leonard WJ

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

June 7, 2011

Associated Grants

  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • 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