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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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
June 2025
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| In: |
Journal of advanced research
Year: 2025, Jahrgang: 72, Pages: 401420 |
| ISSN: | 20901224 |
| DOI: | 10.1016/j.jare.2024.07.007 |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 245 | 1 | 0 | |a C-reactive protein orchestrates acute allograft rejection in vascularized composite allotransplantation via selective activation of monocyte subsets |c 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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| 520 | |a 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. | ||
| 650 | 4 | |a Allograft rejection | |
| 650 | 4 | |a C-reactive protein | |
| 650 | 4 | |a Monocytes | |
| 650 | 4 | |a Vascularized composite allotransplantation | |
| 700 | 1 | |a Zeller, Johannes |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schneider, Laura |e VerfasserIn |4 aut | |
| 700 | 1 | |a Thomé, Julia |e VerfasserIn |4 aut | |
| 700 | 1 | |a McFadyen, James D. |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Woollard, Kevin J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pomahac, Bohdan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Peter, Karlheinz |e VerfasserIn |4 aut | |
| 700 | 1 | |8 4\p |a Eisenhardt, Steffen Ulrich |d 1978- |e VerfasserIn |0 (DE-588)132976986 |0 (DE-627)529563924 |0 (DE-576)299540243 |4 aut | |
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