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C-reactive protein orchestrates acute allograft rejection in vascularized composite allotransplantation via selective activation of monocyte subsets

Introduction - Despite advancements in transplant immunology and vascularized composite allotransplantation (VCA), the longevity of allografts remains hindered by the challenge of allograft rejection. The acute-phase response, an immune-inflammatory reaction to ischemia/reperfusion that occurs direc...

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Main Authors: Kiefer, Jurij (Author) , Zeller, Johannes (Author) , Schneider, Laura (Author) , Thomé, Julia (Author) , McFadyen, James D. (Author) , Hörbrand, Isabel (Author) , Lang, Friederike (Author) , Deiss, Emil (Author) , Bogner, Balázs (Author) , Schaefer, AnnaLena (Author) , Chevalier, Nina (Author) , Horner, Verena K. (Author) , Kreuzaler, Sheena (Author) , Kneser, Ulrich (Author) , KaukeNavarro, Martin (Author) , Braig, David Johannes (Author) , Woollard, Kevin J. (Author) , Pomahac, Bohdan (Author) , Peter, Karlheinz (Author) , Eisenhardt, Steffen Ulrich (Author)
Format: Article (Journal)
Language:English
Published: June 2025
In: Journal of advanced research
Year: 2025, Volume: 72, Pages: 401420
ISSN:20901224
DOI:10.1016/j.jare.2024.07.007
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jare.2024.07.007
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2090123224002911
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Author Notes:Jurij Kiefer, Johannes Zeller, Laura Schneider, Julia Thomé, James D. McFadyen, Isabel A. Hoerbrand, Friederike Lang, Emil Deiss, Balázs Bogner, Anna-Lena Schaefer, Nina Chevalier, Verena K. Horner, Sheena Kreuzaler, Ulrich Kneser, Martin Kauke-Navarro, David Braig, Kevin J. Woollard, Bohdan Pomahac, Karlheinz Peter, Steffen U. Eisenhardt
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Summary:Introduction - Despite advancements in transplant immunology and vascularized composite allotransplantation (VCA), the longevity of allografts remains hindered by the challenge of allograft rejection. The acute-phase response, an immune-inflammatory reaction to ischemia/reperfusion that occurs directly after allogeneic transplantation, serves as a catalyst for graft rejection. This immune response is orchestrated by acute-phase reactants through intricate crosstalk with the mononuclear phagocyte system. - Objective - C-reactive protein (CRP), a well-known marker of inflammation, possesses pro-inflammatory properties and exacerbates ischemia/reperfusion injury. Thus, we investigated how CRP impacts acute allograft rejection. - Methods - Prompted by clinical observations in facial VCAs, we employed a complex hindlimb transplantation model in rats to investigate the direct impact of CRP on transplant rejection. - Results - Our findings demonstrate that CRP expedites allograft rejection and diminishes allograft survival by selectively activating non-classical monocytes. Therapeutic stabilization of CRP abrogates this activating effect on monocytes, thereby attenuating acute allograft rejection. Intravital imagining of graft-infiltrating, recipient-derived monocytes during the early phase of acute rejection corroborated their differential regulation by CRP and their pivotal role in driving the initial stages of graft rejection. - Conclusion - The differential activation of recipient-derived monocytes by CRP exacerbates the innate immune response and accelerates clinical allograft rejection. Thus, therapeutic targeting of CRP represents a novel and promising strategy for preventing acute allograft rejection and potentially mitigating chronic allograft rejection.
Item Description:Online verfügbar: 9. Juli 2024, Artikelversion: 19. Mai 2025
Gesehen am 15.09.2025
Physical Description:Online Resource
ISSN:20901224
DOI:10.1016/j.jare.2024.07.007

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