June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Effect of sCD83 on macrophages in corneal high-risk transplantation
Author Affiliations & Notes
  • Alfrun Schönberg
    Experimental Ophthalmology, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Katrin Peckert-Maier
    Department of Immune Modulation, University Hospital Erlangen, Erlangen, Bavaria, Germany
  • Andreas Wild
    Department of Immune Modulation, University Hospital Erlangen, Erlangen, Bavaria, Germany
  • Dmytro Royzman
    Department of Immune Modulation, University Hospital Erlangen, Erlangen, Bavaria, Germany
  • Gabriele Braun
    Experimental Ophthalmology, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Lena Stich
    Department of Immune Modulation, University Hospital Erlangen, Erlangen, Bavaria, Germany
  • Claus Cursiefen
    Experimental Ophthalmology, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Alexander Steinkasserer
    Department of Immune Modulation, University Hospital Erlangen, Erlangen, Bavaria, Germany
  • Felix Bock
    Experimental Ophthalmology, Uniklinik Koln, Koln, Nordrhein-Westfalen, Germany
  • Elisabeth Zinser
    Department of Immune Modulation, University Hospital Erlangen, Erlangen, Bavaria, Germany
  • Footnotes
    Commercial Relationships   Alfrun Schönberg, None; Katrin Peckert-Maier, None; Andreas Wild, None; Dmytro Royzman, None; Gabriele Braun, None; Lena Stich, None; Claus Cursiefen, None; Alexander Steinkasserer, None; Felix Bock, None; Elisabeth Zinser, None
  • Footnotes
    Support  DFG Research Unit BO4489/1-2, BO4489/3-1, ZI1225/1-1, Center for Molecular Medicine Cologne (CMMC), CRC1181 (Project B03)
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 909. doi:
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    • Get Citation

      Alfrun Schönberg, Katrin Peckert-Maier, Andreas Wild, Dmytro Royzman, Gabriele Braun, Lena Stich, Claus Cursiefen, Alexander Steinkasserer, Felix Bock, Elisabeth Zinser; Effect of sCD83 on macrophages in corneal high-risk transplantation. Invest. Ophthalmol. Vis. Sci. 2021;62(8):909.

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

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Abstract

Purpose : Severe inflammation of the cornea abrogates its immunological and angiogenic privilege and eventually leads to corneal blindness. Under these high-risk conditions, vision-restoring corneal transplants have dramatically reduced chances for graft acceptance. Pro-inflammatory macrophages comprise 60 % of all infiltrating immune cells in a rejected graft. We hypothesize that administration of the immunomodulatory protein sCD83 leads to a shift from pro-inflammatory classically activated macrophages (CAM), characterized among others by TNF-α, IL-6 and CD86 expression, to anti-inflammatory alternatively activated macrophages (AAM), characterized among others by CCL22, CCL17, and MSR-1 expression, and thereby promotes corneal graft acceptance.

Methods : In a model of high-risk corneal transplantation (C57BL/6 donor and BALB/c recipient mice), 50 µg/ml sCD83 was administered locally 2 days prior to keratoplasty (KPL). Macrophages in the draining lymph nodes (dLNs) of the recipient were analyzed by flow cytometry 2 weeks post KPL. The allograft survival was determined by grading the opacity of the grafts weekly for 8 weeks. sCD83 was also administered during cultivation of BMDMs and its effect analyzed in flow cytometry and MLR experiments.

Results : In the dLNs of sCD83-treated recipients, the frequency of MSR-1+ AAMs was significantly increased while significant less CD86+ CAMs were detected 2 weeks post KPL. 8 weeks post KPL, the number of Foxp3+ Tregs in the dLNs was increased and the graft survival was significantly higher in the sCD83 group. In vitro, sCD83 induced a tolerogenic phenotype in BMDMs as the expression of CCL17, CCL22 and MSR-1 was significantly upregulated while the expression of CD83 and CD86 was significantly downregulated. In co-culture experiments showed sCD83-treated BMDMs an impaired ability to induce allogeneic T cell proliferation while increased numbers of Foxp3+ Tregs were detected. TNF-α as well as IL-6 concentrations were decreased in co-culture supernatants when BMDMs were treated with sCD83.

Conclusions : Our results are consistent with our hypothesis that administration of sCD83 leads to a shift from CAM to AAM which prolongs allograft survival in a high-risk corneal transplantation model. Thereby, we not only confirmed the important role of macrophages in the transplant setting, but also demonstrated the beneficial potential of their modulation by sCD83 to prolong corneal graft survival.

This is a 2021 ARVO Annual Meeting abstract.

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