April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Galectin-8 inhibits experimental autoimmune uveitis by promoting regulatory T cells
Author Affiliations & Notes
  • James Sampson
    Tufts University, Boston, MA
  • Amol Suryawanshi
    Tufts University, Boston, MA
  • Wei-Sheng Chen
    Tufts University, Boston, MA
  • Lama Mulki
    Massachusetts Eye and Ear Institute, Boston, MA
  • Eiichi Hasegawa
    Massachusetts Eye and Ear Institute, Boston, MA
  • Kip M Connor
    Massachusetts Eye and Ear Institute, Boston, MA
  • Gabriel A Rabinovich
    Institute of Biology and Experimental Medicine, CONICET, Buenos Aires, Argentina
  • Noorjahan A Panjwani
    Tufts University, Boston, MA
  • Footnotes
    Commercial Relationships James Sampson, None; Amol Suryawanshi, None; Wei-Sheng Chen, None; Lama Mulki, None; Eiichi Hasegawa, None; Kip Connor, None; Gabriel Rabinovich, None; Noorjahan Panjwani, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4601. doi:
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      James Sampson, Amol Suryawanshi, Wei-Sheng Chen, Lama Mulki, Eiichi Hasegawa, Kip M Connor, Gabriel A Rabinovich, Noorjahan A Panjwani; Galectin-8 inhibits experimental autoimmune uveitis by promoting regulatory T cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4601.

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

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Abstract

Purpose: Galectins (gal) such as gal-1 and gal-9 have been shown to play an immunomodulatory role by inhibiting effector T cells and promoting regulatory T cells (Treg), however the role of gal-8 in T cell homeostasis is poorly understood. Experimental autoimmune uveitis (EAU) is a mouse model of uveitis that is driven by Th17 cells. Pathology can be ameliorated by shifting the T cell response from Th17 to Treg. Thus, the purpose of this study is to determine what role gal-8 plays in T cell differentiation, and to determine whether gal-8 treatment reduces EAU pathology.

Methods: Mouse CD4+ T cells were isolated by negative selection and polarized to Th1, Th2, Th17, and Treg in the presence and absence of recombinant gal-8 to determine the effects of gal-8 on T cell differentiation. In order to identify novel gal-8 binding partners, the effects of gal-8 on IL-2 receptor and TGFβ receptor signaling, necessary for Treg polarization, were determined by western blotting. The ability of Tregs to inhibit proliferation of activated T cells was assessed in in vitro suppression assays. EAU was actively induced by immunization with IRBP1-20, and one group of mice were treated with vehicle, while the other group was treated with gal-8.

Results: Recombinant gal-8 promoted Th2 and Treg differentiation and induced apoptosis of Th17 cells in vitro. Gal-8 sustained STAT5 phosphorylation downstream of IL-2 receptor, and enhanced Smad3 phosphorylation downstream of TGFβ receptor to promote Treg polarization. Tregs polarized in the presence of gal-8 suppressed division of activated T cells. Treatment of uveitic mice with gal-8 resulted in significantly delayed pathology and expanded Tregs in draining lymph nodes.

Conclusions: Gal-8 induces apoptosis of Th17 cells and promotes Treg differentiation, making it a good candidate for treating human uveitis without the side effects of long-term corticosteroids or immunosuppressive drugs.

Keywords: 555 immunomodulation/immunoregulation • 746 uveitis-clinical/animal model • 490 cytokines/chemokines  
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