B Cell‐Mediated Maintenance of Cluster of Differentiation 169–Positive Cells Is Critical for Liver Regeneration. Issue 6 (5th November 2018)

• Record Type: Journal Article
• Authors: Behnke, Kristina; Zhuang, Yuan; Xu, Haifeng C.; Sundaram, Balamurugan; Reich, Maria; Shinde, Prashant V.; Huang, Jun; Modares, Nastaran Fazel; Tumanov, Alexei V.; Polz, Robin; Scheller, Jürgen; Ware, Carl F.; Pfeffer, Klaus; Keitel, Verena; Häussinger, Dieter; Pandyra, Aleksandra A.; Lang, Karl S.; Lang, Philipp A.
• Is Part Of: Hepatology. Volume 68:Issue 6(2018)
• Page Start: 2348
• Page End: 2361
• Publication Date: 2018-11-05
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.30088
• Languages: English
• ISSNs: 0270-9139

Abstract

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.