April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Similarities of human EMR2 to mouse F4/80 in ocular tolerance
Author Affiliations & Notes
  • Helen Song
    Schepens Eye Research Institute, Boston, MA
  • Siamon Gordon
    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
  • Joan Stein-Streilein
    Schepens Eye Research Institute, Boston, MA
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3576. doi:
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      Helen Song, Siamon Gordon, Joan Stein-Streilein; Similarities of human EMR2 to mouse F4/80 in ocular tolerance. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3576.

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

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Abstract

Purpose: In the mouse, F4/80 protein on macrophages is required for the development of Treg cells in two models of tolerance, the eye and gut. It has been demonstrated that an intact spleen is necessary for ocular tolerance in vivo. Since F4/80 is not expressed in humans, the purpose of this research is to determine the human analog of F4/80. F4/80 belongs to a novel family of EGF-TM7 molecules which includes the EMR subset. In the human, EMR1 has sequential homology with F4/80 and EMR2 has immune suppressing function in tumor cells. Thus, we investigate the possible suppressor role of the EMR family in human ocular tolerance.

Methods: Human peripheral blood mononuclear cells (huPBMC) were treated with TGFβ2 and LPS or Diphtheria Toxoid (DT) for at least six hours to generate tolerogenic APC. Cells were characterized by flow cytometric analysis for expression of CD14, CD40, PDL1, ILT3, EMR1, and EMR2. Later, Treg cells were generated by incubating tolerogenic APC with autologous huPBMC for 5-7 days. Post culture, T cells were immunostained and characterized for expression of CD4, CD25, and FoxP3.

Results: Post treatment of huPBMC with TGFβ2 and LPS or DT, the resulting tolerogenic APC expressed PDL1, ILT3, and EMR2. CD40 remained unchanged and CD14 was constitutively expressed. Post 5-7 day culture, tolerogenic APC treated with TGFβ2 increased the CD4+ CD25+ FoxP3+ lymphocyte populations.

Conclusions: The upregulation of EMR2 on human tolerogenic APC suggests that EMR2 may have a role in inducing tolerance in humans. Current studies are analyzing the role of EMR2 in the generation and function of Treg cells. Once the F4/80 analog is established for humans, novel therapies may be developed to interfere or encourage in the treatment of tumors or immune inflammatory diseases, respectively.

Keywords: 423 antigen presentation/processing • 553 immune tolerance/privilege  
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