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DOI: 10.1055/s-0038-1677107
B cell-mediated maintenance of CD169+ cells is critical for liver regeneration
Publikationsverlauf
Publikationsdatum:
04. Januar 2019 (online)
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.