Pre-incubation of corneal donor tissue with sCD83 improves graft survival via the induction of alternatively activated macrophages and tolerogenic dendritic cells

Peckert-Maier K, Schoenberg A, Wild A, Royzman D, Braun G, Stich L, Hadrian K, Tripal P, Cursiefen C, Steinkasserer A, Zinser E, Bock F (2021)

Publication Type: Journal article

Publication year: 2021

Journal

DOI: 10.1111/ajt.16824

Abstract

Immune responses reflect a complex interplay of cellular and extracellular components which define the microenvironment of a tissue. Therefore, factors that locally influence the microenvironment and re-establish tolerance might be beneficial to mitigate immune-mediated reactions, including the rejection of a transplant. In this study, we demonstrate that pre-incubation of donor tissue with the immune modulator soluble CD83 (sCD83) significantly improves graft survival using a high-risk corneal transplantation model. The induction of tolerogenic mechanisms in graft recipients was achieved by a significant upregulation of Tgfb, Foxp3, II27, and II10 in the transplant and an increase of regulatory dendritic cells (DCs), macrophages (M phi) and T cells (Tregs) in eye-draining lymph nodes. The presence of sCD83 during in vitro DC and M phi generation directed these cells toward a tolerogenic phenotype leading to reduced proliferation-stimulating activity in MLRs. Mechanistically, sCD83 induced a tolerogenic M phi and DC phenotype, which favors Treg induction and significantly increased transplant survival after adoptive cell transfer. Conclusively, pre-incubation of corneal grafts with sCD83 significantly prolongs graft survival by modulating recipient M phi and DCs toward tolerance and thereby establishing a tolerogenic microenvironment. This functional strategy of donor graft pre-treatment paves the way for new therapeutic options in the field of transplantation.

Authors with CRIS profile

Involved external institutions

Universität zu Köln Germany (DE)

How to cite

APA:

Peckert-Maier, K., Schoenberg, A., Wild, A., Royzman, D., Braun, G., Stich, L.,... Bock, F. (2021). Pre-incubation of corneal donor tissue with sCD83 improves graft survival via the induction of alternatively activated macrophages and tolerogenic dendritic cells. American Journal of Transplantation. https://dx.doi.org/10.1111/ajt.16824

MLA:

Peckert-Maier, Katrin, et al. "Pre-incubation of corneal donor tissue with sCD83 improves graft survival via the induction of alternatively activated macrophages and tolerogenic dendritic cells." American Journal of Transplantation (2021).

BibTeX: Download