June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Contribution of Th1 and Th17 lineage cytokines to pathogenesis of ocular autoimmunity
Author Affiliations & Notes
  • So Jin Bing
    Immunoregulation section, National Eye Institute, Bethesda, Maryland, United States
  • Reiko Horai
    Immunoregulation section, National Eye Institute, Bethesda, Maryland, United States
  • Phyllis Silver
    Immunoregulation section, National Eye Institute, Bethesda, Maryland, United States
  • Yingyos Jittayasothorn
    Immunoregulation section, National Eye Institute, Bethesda, Maryland, United States
  • Jun Chen
    Immunoregulation section, National Eye Institute, Bethesda, Maryland, United States
  • Chi-Chao Chan
    Immunoregulation section, National Eye Institute, Bethesda, Maryland, United States
  • Rachel R Caspi
    Immunoregulation section, National Eye Institute, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   So Jin Bing, None; Reiko Horai, None; Phyllis Silver, None; Yingyos Jittayasothorn, None; Jun Chen, None; Chi-Chao Chan, None; Rachel Caspi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 545. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      So Jin Bing, Reiko Horai, Phyllis Silver, Yingyos Jittayasothorn, Jun Chen, Chi-Chao Chan, Rachel R Caspi; Contribution of Th1 and Th17 lineage cytokines to pathogenesis of ocular autoimmunity
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):545.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Retina-specific IFN-γ- secreting Th1 cells and IL-17A-secreting Th17 cells are pathogenic effectors in uveitis. However, their respective contributions to disease are not fully understood. In this study, we used an active immunization model of experimental autoimmune uveitis (EAU) and the IRBP T cell receptor transgenic spontaneous uveitis model (R161H) on the B10.RIII background to dissect the role of Th1 and Th17 subsets and their lineage-specific cytokines in pathogenesis of uveitis.

Methods : We introgressed the retina-specific R161H TCR onto IL-17A-/-, IFN-γ-/- (=GKO) and IL-17/IFN-g double knockout (DKO) backgrounds. In addition, EAU was induced by immunization in DKO mice with a normal T cell repertoire, treated, or not, with blocking antibodies to IL-17F, TNF-a, IL-22 or GM-CSF.

Results : R161H-IL-17A-/- mice developed spontaneous uveitis of similar severity to R161H mice. In contrast, R161H-GKO mice developed significantly attenuated disease with delayed onset, suggesting that IFN-γ, but not IL-17A, is a critical pathogenic cytokine in this model. Surprisingly, R161H mice deficient in both IL-17A and IFN-γ developed more severe disease than R161H-GKO mice, although the onset of disease appeared to be delayed. DKO mice were also susceptible to EAU induced by active immunization. Blockade of IL-17F, TNF-a, or IL-22 in DKO mice did not affect the outcome of EAU, suggesting that these cytokines are dispensable for development of EAU in this model. However, treatment of DKO mice with anti-GM-CSF either as prevention or as a reversal paradigm significantly suppressed EAU, suggesting that GM-CSF may play a major pathogenic role in ocular autoimmune disease when IFN-γ and IL-17A are both absent.

Conclusions : These results suggest that Th1 and Th17 cells are dispensable as pathogenic effectors in uveitis. In their absence, other inflammatory cytokine(s) such as GM-CSF, can also contribute to development of disease. Further mechanistic studies may uncover novel effector pathway(s) in pathogenesis of ocular autoimmunity.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×