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Immune checkpoints TIM-3 and Gal-9 are upregulated in male placentas with acute SARS-CoV-2 infection

New data indicate an increased risk of obstetric complications after Covid-19, the aim of this study was therefore to investigate the expression of immune checkpoint molecules TIM-3 and Gal-9 in tissue sections of placenta from patients with acute Covid-19, from patients after Covid-19 infection and...

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Main Authors: Seefried, Marina (Author) , Lurtz, Ines (Author) , Mittelberger, Johanna (Author) , Franitza, Manuela (Author) , Bubmann, Jonas (Author) , Wild, Carl Mathis (Author) , Ditsch, Nina (Author) , Urban, Birgit (Author) , Kuhn, Christina (Author) , Dannecker, Christian (Author) , Altevogt, Peter (Author) , Jeschke, Udo (Author) , Sammar, Marei (Author)
Format: Article (Journal)
Language:English
Published: December 2025
In: Journal of reproductive immunology
Year: 2025, Volume: 172, Pages: 1-12
ISSN:1872-7603
DOI:10.1016/j.jri.2025.104797
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jri.2025.104797
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0165037825003754
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Author Notes:Marina C. Seefried, Ines Lurtz, Johanna Mittelberger, Manuela Franitza, Jonas Bubmann, Carl Mathis Wild, Nina Ditsch, Birgit Urban, Christina Kuhn, Christian Dannecker, Peter Altevogt, Udo Jeschke, Marei Sammar
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Summary:New data indicate an increased risk of obstetric complications after Covid-19, the aim of this study was therefore to investigate the expression of immune checkpoint molecules TIM-3 and Gal-9 in tissue sections of placenta from patients with acute Covid-19, from patients after Covid-19 infection and from healthy controls. We used a total of 60 placentas from women who had given birth to female or male children at Augsburg University Hospital, Germany. We examined 10 placentas each with acute Covid-19 from female and male fetuses, 10 placentas each from female and male fetuses after acute Covid-19 and 10 placentas each from female and male fetuses of a healthy control group. Immunohistochemical staining against TIM-3 and Gal-9 was performed, and marker expression was assessed by an immunoreactive score (IRS). The identity of cells expressing TIM-3 or Gal-9 was then analyzed by double immunofluorescence analysis. TIM-3- and Gal-9 positive macrophages are significantly upregulated in the decidua of female acute Covid-19 placentas. TIM-3 is significantly up-regulated in male extravillous trophoblast cells in the acute phase of Covid-19. On the other hand, TIM-3 was significantly downregulated in Hofbauer cells from male placentas after Covid-19. Gal-9, the ligand for TIM-3, was significantly downregulated in Hofbauer cells from male placentas after Covid-19. Triple immunofluorescence analysis showed that male acute Covid-19 Hofbauer cells (analyzed by CD163 staining) were positive for both TIM-3 and Gal-9. Surprisingly, the observed effects were related to fetal sex. In particular, the formative effect of this infection needs to be analyzed in further studies.
Item Description:Online verfügbar 28 October 2025, Version des Artikels 3 November 2025
Gesehen am 17.03.2026
Physical Description:Online Resource
ISSN:1872-7603
DOI:10.1016/j.jri.2025.104797

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