Universität zu Köln

Peckert-Maier, Katrin ORCID: 0000-0001-8258-0691, Schoenberg, Alfrun, Wild, Andreas B., Royzman, Dmytro, Braun, Gabriele, Stich, Lena, Hadrian, Karina, Tripal, Philipp ORCID: 0000-0003-0568-1725, Cursiefen, Claus, Steinkasserer, Alexander, Zinser, Elisabeth and Bock, Felix (2022). Pre-incubation of corneal donor tissue with sCD83 improves graft survival via the induction of alternatively activated macrophages and tolerogenic dendritic cells. Am. J. Transplant., 22 (2). S. 438 - 455. HOBOKEN: WILEY. ISSN 1600-6143

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Peckert-Maier, Katrin UNSPECIFIED orcid.org/0000-0001-8258-0691 UNSPECIFIED Schoenberg, Alfrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Wild, Andreas B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Royzman, Dmytro UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Stich, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Hadrian, Karina UNSPECIFIED UNSPECIFIED UNSPECIFIED Tripal, Philipp UNSPECIFIED orcid.org/0000-0003-0568-1725 UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinkasserer, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Zinser, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-576573
DOI:	10.1111/ajt.16824
Journal or Publication Title:	Am. J. Transplant.
Volume:	22
Number:	2
Page Range:	S. 438 - 455
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1600-6143
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language T-CELLS; CD83; REJECTION; TOLERANCE; RECEPTOR; SURFACE; PREVENTION; PATHWAY; COMPLEX Multiple languages Surgery; Transplantation Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57657