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.

KEYWORDS:

• liver regeneration
• proliferation
• IL-6
• IL-17
• IL-17RA
• A20

Acknowledgments

We wish to thank Damiano Scopetti for the fruitful discussion, Silvano Pagnotta and Maria Luisa Alunni for technical support. The original studies (to G. S.) were supported in part by Associazione Umbra Contro il Cancro (AUCC), PRIN Project n. 20152CB22L_004, Fondazione Cassa di Risparmio di Perugia 2015.0329.021, Comitato Maria Grazia Frasconi. DP, SP, MC and DB are recipient of the AUCC fellowship program.

Disclosure of Interest

The authors report no conflict of interest.

Supplementary material

Supplementary data for this article can be accessed here.

Additional information

Funding

This study was supported by grants from the Associazione Umbra Contro il Cancro (AUCC), Fondazione Cassa di Risparmio di Perugia, n. 2015.0329.021, Comitato Maria Grazia Frasconi. GS is recipient of a PRIN n. 20152CB22L_004 Project. DP, SP, MC and DB are recipient of the AUCC fellowship program.