June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Th1 and Th17 autoimmune responses differ in responding to adenosine receptor (AR) agonists
Author Affiliations & Notes
  • Deming Sun
    DVRC-411, Doheny Eye Institute, Los Angeles, CA
    Ophthalmology, UCLA, Los Angeles, CA
  • Aijun Zuo
    DVRC-411, Doheny Eye Institute, Los Angeles, CA
    Ophthalmology, UCLA, Los Angeles, CA
  • Hui Shao
    Ophthalmology, University of Louisville, Louisville, KY
  • Henry Kaplan
    Ophthalmology, University of Louisville, Louisville, KY
  • Dongchun Liang
    DVRC-411, Doheny Eye Institute, Los Angeles, CA
  • Footnotes
    Commercial Relationships Deming Sun, None; Aijun Zuo, None; Hui Shao, None; Henry Kaplan, None; Dongchun Liang, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 869. doi:
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    • Get Citation

      Deming Sun, Aijun Zuo, Hui Shao, Henry Kaplan, Dongchun Liang; Th1 and Th17 autoimmune responses differ in responding to adenosine receptor (AR) agonists . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):869.

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

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Abstract

Purpose: ATP release together with increased adenosine generation is a general phenomenon in inflammation. Control activation of adenosine receptors has been shown to be beneficial in treating a series of inflammatory and autoimmune disorders. While previous studies mostly examined the effects of AR agonists on Th1-type immune responses, in this study, we compared the effect of AR agonists on Th17 and Th1 autoimmune responses in experimental autoimmune uveitis (EAU).

Methods: EAU was induced in B6 mice by subcutaneous injection of 200 μl of emulsion containing 200 μg of human IRBP1-20 in CFA. aβ and γδ T cells were purified from immunized mice. For NECA treatment, immunized B6 mice received a single i.p. injection of NECA (5 µg/kg) on different days after immunization. The intensity of Th1 and Th17 response and the pathogenic activity of isolated autoreactive T cells were compared between in vivo treated and non-treated mice and between cells with or without AR agonist treatment in vitro.

Results: The effects of NECA on Th1 and Th17 responses were completely dissociated. The enhancing effect of NECA on Th17 responses was modulated by γδ T cells. Activated γδ T cells expressed the highest levels of A2AR receptors. A2AR ligation inhibits αβ T cell activation, but enhances γδ T cell activation. AR agonist promotes the differentiation of a DC subset co-expressing CD11c and Gr-1, which possess a strong stimulating effect on Th17 autoreactive T cells.

Conclusions: AR agonists had a consistent inhibitory effect on the Th1 autoimmune response; however, their effect on the Th17 autoimmune response could be either inhibitory or enhancing, depending on both environmental conditions and the activation status of the T cells. Our results show that the inflammatory environment has a strong impact on converting the effect of AR agonist on the Th17 autoimmune response from anti- to pro-inflammatory. Given that both Th1 and Th17 autoreactive T cells are pathogenic for autoimmune diseases, identification of the mechanisms by which adenosine enhances or inhibits should allow us to minimize the enhancing effect of AR agonists on the Th17 response and improve the therapeutic goal of controlling both Th1 and Th17 responses in autoimmune diseases.

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