Z Gastroenterol 2019; 57(01): e26
DOI: 10.1055/s-0038-1677107
1. Basic Hepatology (Fibrogenesis, NPC, Transport)
Georg Thieme Verlag KG Stuttgart · New York

B cell-mediated maintenance of CD169+ cells is critical for liver regeneration

Authors

  • K Vogel

    1   Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany

  • Y Zhuang

    1   Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany

  • X Haifeng

    1   Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany

  • B Sundaram

    1   Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany

  • J Huang

    1   Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany

  • M Reich

    2   Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany

  • AV Tumanov

    3   Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health Science Center, San Antonio, TX 78229,

  • R Polz

    4   Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany,

  • J Scheller

    4   Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany,

  • CF Ware

    5   Infectious and Inflammatory Diseases Research Center, Sanford Burnham Prebys Medical Discovery Research Institute, La Jolla, CA 92037,

  • K Pfeffer

    6   Institute of Medical Microbiology and Hospital Hygiene, University Hospital, Heinrich-Heine-University, Düsseldorf, Germany,

  • V Keitel

    2   Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany

  • D Häussinger

    2   Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany

  • AA Pandyra

    1   Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany

  • KS Lang

    7   Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, Essen 45147, Germany.

  • PA Lang

    1   Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
04. Januar 2019 (online)

Auch verfügbar auf
 

Introduction:

The liver has an extraordinary capacity to regenerate via activation of key molecular pathways. Loss of at least 30% of liver mass, leads to synchronized proliferation of mature hepatocytes and rapid restoration of liver mass via compensatory hyperplasia. However, central regulators controlling liver regeneration such as the contribution of B cells and CD169+ cells during liver regeneration remain insufficiently studied.

Methods:

To analyze the dynamic processes during liver regeneration, we performed Partial Hepatectomy (PHx) and Splenectomy (Sx) in different Knockout-mice without and after antibody treatment or IL-6/IL-6R injection. Using kinetics we examined the gene expression profile of liver and spleen tissue after PHx. H/E-staining of liver sections and cytokine ELISAs were performed and serum protein levels were analyzed.

Results:

Here we show that B cell-deficient animals failed to induce sufficient liver regeneration after partial hepatectomy (PHx). Consistently, adoptive transfer of B cells could rescue defective liver regeneration. B cell mediated lymphotoxin beta production promoted recovery from PHx. Absence of B cells coincided with loss of splenic CD169+ macrophages. Moreover, depletion of CD169+ cells resulted in defective liver regeneration and decreased survival, which was associated with reduced hepatocyte proliferation. Mechanistically, CD169+ cells contributed to liver regeneration by inducing hepatic IL-6 production. Accordingly, treatment of CD169+ cell depleted animals with IL-6/Il-6R rescued severe pathology following PHx.

In conclusion, we identified CD169+ cells to be a central trigger for liver regeneration, by inducing several key signaling pathways important for liver regeneration.