Liver sinusoidal endothelial cells orchestrate NK cell recruitment and activation in acute inflammatory liver injury
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,
Ana Stojanovic
Affiliations
Sophia Papaioannou
Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Jia-Xiang See
Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Mingeum Jeong
Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Carolina De La Torre
NGS Core Facility, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Volker Ast
NGS Core Facility, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Institute for Clinical Chemistry, University Hospital Mannheim (UMM), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Philipp-Sebastian Reiners-Koch
European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim, Germany
Ankita Sati
CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Clinical Cooperation Unit (CCU), Heidelberg, Germany
Carolin Mogler
Institute of Pathology, Technical University Munich, Munich, Germany
Michael Platten
CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Clinical Cooperation Unit (CCU), Heidelberg, Germany; Department of Neurology, University Hospital Mannheim (UMM), MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany
Adelheid Cerwenka
Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Corresponding author
Ana Stojanovic
Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Corresponding author
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.
