B Cell-Mediated Maintenance of Cluster of Differentiation 169–Positive Cells Is Critical for Liver Regeneration

Kristina Behnke, Yuan Zhuang, Haifeng C. Xu, Balamurugan Sundaram, Maria Reich, Prashant V. Shinde, Jun Huang, Nastaran Fazel Modares, Alexei V. Tumanov, Robin Polz, Jürgen Scheller, Carl F. Ware, Klaus Pfeffer, Verena Keitel, Dieter Häussinger, Aleksandra A. Pandyra, Karl S. Lang, Philipp A. Lang

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The liver has an extraordinary capacity to regenerate through activation of key molecular pathways. However, central regulators controlling liver regeneration remain insufficiently studied. 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 cluster of differentiation 169–positive (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 interleukin-6 (IL-6) production and signal transducer and activator of transcription 3 activation. Accordingly, treatment of CD169 + cell–depleted animals with IL-6/IL-6 receptor rescued liver regeneration and severe pathology following PHx. Conclusion: We identified CD169 + cells to be a central trigger for liver regeneration, by inducing key signaling pathways important for liver regeneration.

Original languageEnglish (US)
Pages (from-to)2348-2361
Number of pages14
JournalHepatology
Volume68
Issue number6
DOIs
StatePublished - Dec 2018

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'B Cell-Mediated Maintenance of Cluster of Differentiation 169–Positive Cells Is Critical for Liver Regeneration'. Together they form a unique fingerprint.

Cite this