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Role of IL-17RA in the proliferative priming of hepatocytes in liver regeneration

ABSTRACT A tight link has been established between inflammation and cancer. Liver regeneration is a widely used model to study the correlation between inflammation and proliferation. IL-6 is essentially involved in liver regeneration and in cancer. Recently, IL-17A has been shown to regulate not only inflammation, but also cell proliferation. Here, we analyze the role played by IL-17A signaling in liver regeneration by comparing cell proliferation in Wild Type and IL-17RA−/− mice. Partial hepatectomy experiments performed in IL-17RA−/− mice showed a delay in expression of early-genes to prime the residual hepatocyte to proliferate, with subsequent delay in G1/S-phase transition. We demonstrated that IL-17RA regulates, by recruitment of non-parenchymal cell, the expression of IL-6, which in turn triggers the proliferation of residual hepatocytes. Our data indicate an important role played by IL-17RA in liver proliferation via IL-6.