Abstract
Molecular mechanisms that modulate liver regeneration are of critical importance for a number of hepatic disorders. Kupffer cells and natural killer (NK) cells are two cell subsets indispensable for liver regeneration. We have focused on these two populations and, in particular, the interplay between them. Importantly, we demonstrate that deletion of the myeloid phosphatase and tensin homolog on chromosome 10 (PTEN) leading to an M2-like polarization of Kupffer cells, which results in decreased activation of NK cells. In addition, PTEN-deficient Kupffer cells secrete additional factors that facilitate the proliferation of hepatocytes. In conclusion, PTEN is critical for inhibiting M2-like polarization of Kupffer cells after partial hepatectomy, resulting in NK cell activation and thus the inhibition of liver regeneration. Furthermore, PTEN reduces growth factor secretion by Kupffer cells. Our results suggest that targeting PTEN on Kupffer cells may be useful in altering liver regeneration in patients undergoing liver resection.
Highlights
Liver regeneration is the compensatory hyperplasia of the liver in response to injury
A recent study suggests that deficiency of the co-inhibitory receptor TIGIT on natural killer (NK) cells leads to overactivation and potentially impedes liver regeneration.[5]
In support of this hypothesis, we demonstrate that myeloid phosphatase and tensin homolog on chromosome 10 (PTEN) deficiency results in an M2-like polarization of Kupffer cells, which are less able to activate NK cells and alter regeneration
Summary
Liver regeneration is the compensatory hyperplasia of the liver in response to injury During this process, the innate immune system, Kupffer cells and natural killer (NK) cells, has a fundamental role. We propose that a better understanding of the interplay of Kupffer cells and NK cells is essential to understand the molecular events that modulate liver regeneration. In support of this hypothesis, we demonstrate that myeloid PTEN deficiency results in an M2-like polarization of Kupffer cells, which are less able to activate NK cells and alter regeneration. This study may provide a potential target for promoting improved liver regeneration following liver resection
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