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Liver sinusoidal endothelial cells orchestrate NK cell recruitment and activation in acute inflammatory liver injury

Liver sinusoidal endothelial cells (LSECs) rapidly clear lipopolysaccharide (LPS) from the bloodstream and establish intimate contact with immune cells. However, their role in regulating liver inflammation remains poorly understood. We show that LSECs modify their chemokine expression profile driven...

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Main Authors: Papaioannou, Sophia (Author) , See, Jia-Xiang (Author) , Jeong, Mingeum (Author) , Torre, Carolina de la (Author) , Ast, Volker (Author) , Reiners-Koch, Philipp-Sebastian (Author) , Sati, Ankita (Author) , Mogler, Carolin (Author) , Platten, Michael (Author) , Cerwenka, Adelheid (Author) , Stojanovic, Ana (Author)
Format: Article (Journal)
Language:English
Published: 29 August 2023
In: Cell reports
Year: 2023, Volume: 42, Issue: 8, Pages: 1-19
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112836
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.celrep.2023.112836
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124723008471
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Author Notes:Sophia Papaioannou, Jia-Xiang See, Mingeum Jeong, Carolina De La Torre, Volker Ast, Philipp-Sebastian Reiners-Koch, Ankita Sati, Carolin Mogler, Michael Platten, Adelheid Cerwenka, and Ana Stojanovic
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Summary:Liver sinusoidal endothelial cells (LSECs) rapidly clear lipopolysaccharide (LPS) from the bloodstream and establish intimate contact with immune cells. However, their role in regulating liver inflammation remains poorly understood. We show that LSECs modify their chemokine expression profile driven by LPS or interferon-γ (IFN-γ), resulting in the production of the myeloid- or lymphoid-attracting chemokines CCL2 and CXCL10, respectively, which accumulate in the serum of LPS-challenged animals. Natural killer (NK) cell exposure to LSECs in vitro primes NK cells for higher production of IFN-γ in response to interleukin-12 (IL-12) and IL-18. In livers of LPS-injected mice, NK cells are the major producers of this cytokine. In turn, LSECs require exposure to IFN-γ for CXCL10 expression, and endothelial-specific Cxcl10 gene deletion curtails NK cell accumulation in the inflamed livers. Thus, LSECs respond to both LPS and immune-derived signals and fuel a positive feedback loop of immune cell attraction and activation in the inflamed liver tissue.
Item Description:Online verfügbar: 19. Juli 2023
Gesehen am 05.10.2023
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112836

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