TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1

Nat Med. 2007 Jun;13(6):711-8. doi: 10.1038/nm1585. Epub 2007 May 13.


T-helper type 17 cells (T(H)17) are implicated in rodent models of immune-mediated diseases. Here we report their involvement in human uveitis and scleritis, and validate our findings in experimental autoimmune uveoretinitis (EAU), a model of uveitis. T(H)17 cells were present in human peripheral blood mononuclear cells (PBMC), and were expanded by interleukin (IL)-2 and inhibited by interferon (IFN)-gamma. Their numbers increased during active uveitis and scleritis and decreased following treatment. IL-17 was elevated in EAU and upregulated tumor necrosis factor (TNF)-alpha in retinal cells, suggesting a mechanism by which T(H)17 may contribute to ocular pathology. Furthermore, IL-27 was constitutively expressed in retinal ganglion and photoreceptor cells, was upregulated by IFN-gamma and inhibited proliferation of T(H)17. These findings suggest that T(H)1 cells may mitigate uveitis by antagonizing the T(H)17 phenotype through the IFN-gamma-mediated induction of IL-27 in target tissue. The finding that IL-2 promotes T(H)17 expansion provides explanations for the efficacy of IL-2R antibody therapy in uveitis, and suggests that antagonism of T(H)17 by IFN-gamma and/or IL-27 could be used for the treatment of chronic inflammation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Validation Study

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • Cell Proliferation*
  • Cells, Cultured
  • Coculture Techniques
  • Growth Inhibitors / physiology*
  • Humans
  • Interleukin-2 / physiology*
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Interleukins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Organ Culture Techniques
  • STAT1 Transcription Factor / physiology*
  • Scleritis / immunology
  • Scleritis / metabolism
  • Scleritis / pathology*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Uveitis / immunology
  • Uveitis / metabolism
  • Uveitis / pathology*


  • Growth Inhibitors
  • Il27 protein, mouse
  • Interleukin-2
  • Interleukins
  • MYDGF protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Stat1 protein, mouse