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Heme oxygenase-1 modulates CD62E-dependent endothelial cell-monocyte interactions and mitigates HLA-I-induced transplant vasculopathy in mice

The main risk factor for developing transplant vasculopathy (TV) after solid organ transplantation is de-novo production of donor-specific antibodies (DSAs) binding to endothelial cells (ECs) within the graft's vasculature. Diverse leukocyte populations recruited into the vessel wall via activa...

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Main Authors: Schuster, Laura (Author) , Zaradzki, Marcin (Author) , Janßen, Henrike (Author) , Gallenstein, Nadia (Author) , Etheredge, Melanie (Author) , Hofmann, Ilse (Author) , Weigand, Markus A. (Author) , Immenschuh, Stephan (Author) , Larmann, Jan (Author)
Format: Article (Journal)
Language:English
Published: 07 March 2025
In: Frontiers in immunology
Year: 2025, Volume: 16, Pages: 1-18
ISSN:1664-3224
DOI:10.3389/fimmu.2025.1447319
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2025.1447319
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Author Notes:Laura Schuster, Marcin Zaradzki, Henrike Janssen, Nadia Gallenstein, Melanie Etheredge, Ilse Hofmann, Markus A. Weigand, Stephan Immenschuh and Jan Larmann
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Summary:The main risk factor for developing transplant vasculopathy (TV) after solid organ transplantation is de-novo production of donor-specific antibodies (DSAs) binding to endothelial cells (ECs) within the graft's vasculature. Diverse leukocyte populations recruited into the vessel wall via activated ECs contribute to vascular inflammation. Subsequent smooth muscle cell proliferation results in intima hyperplasia, the pathophysiological correlate of TV. We demonstrated that incubating aortic EC with anti-HLA-I antibodies led to increased monocyte adhesion to and transmigration across an EC monolayer. Both occurred in a CD62E-dependent fashion and were sensitive toward the anti-inflammatory enzyme heme oxygenase (HO)-1 modulation. Using a murine heterotopic aortic transplantation model, we demonstrated that anti-MHC I antibody-induced TV is ameliorated by pharmacologically induced HO-1 and the application of anti-CD62E antibodies results in a deceleration of developing TV. HO-1 modulation is a promising therapeutic approach to prevent leukocyte recruitment and subsequent intima hyperplasia in TV and thus precludes organ failure.
Item Description:Gesehen am 30.10.2025
Physical Description:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2025.1447319

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