The anti-fibrotic role of mast cells in the liver is mediated by HLA-G and interaction with hepatic stellate cells

Laurence Amiot (1, 2) , Nicolas Vu (1, 3) , Bernard Drenou (4) , Maurice Scrofani (4) , Arnaud Chalin (1, 3) , Christelle Devisme (1, 3) , Michel Samson (1, 3)

1 Irset - Institut de recherche en santé, environnement et travail
2 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
3 EHESP - École des Hautes Études en Santé Publique [EHESP]
4 CH E.Muller Mulhouse - Centre Hospitalier Emile Muller [Mulhouse]

Background & aims - We have reported a significant association between HLA-G expression or the number of hepatic mast cells and liver fibrosis. Here, we investigated the role of HLA-G and mast cells in liver fibrosis, focusing, in particular, on interactions between human mast and stellate cells. Methods - Human mast cells (HMC cell line, CD34-derived mast cells, or tissue-derived mast cells) were co-cultured with purified human hepatic stellate cells (HSCs), and collagen I production by HSCs was evaluated. Mast cells and HSCs were characterized by immunocytochemistry. Various conditions were tested: different times in direct or indirect contact, presence or absence of cytokines, addition or not of HLA-G, and presence or absence of specific protease inhibitors. Results - The reciprocal interaction between HSCs and mast cells led to the attraction of mast cells to HSCs in vivo and in vitro, and to a significant decrease in collagen production, at all times of co-culture, following the direct or indirect contact of mast cells with HSCs alone or in the presence of TGF-β, IFN-α or IL-10. We identified the diffusible factors involved in collagen I degradation as mast cell proteases. Moreover, HLA-G expression increased during the co-culture of HSCs and mast cells, with HLA-G acting on both mast cells and HSCs, to enhance collagen I degradation. Conclusions - Mast cells play a beneficial, anti-fibrotic role in liver fibrosis, via the HLA-G-mediated decrease of collagen I. These findings are consistent with high levels of cross-communication between mast cells and hepatic stellate cells and the role of HLA-G.

Mots clés: Hepatic stellate cells; Mast cells; Fibrosis; HLA-G

Domaines: Santé

Laurence Amiot, Nicolas Vu, Bernard Drenou, Maurice Scrofani, Arnaud Chalin, et al.. The anti-fibrotic role of mast cells in the liver is mediated by HLA-G and interaction with hepatic stellate cells. Cytokine, 2019, 117, pp.50-58. ⟨10.1016/j.cyto.2019.02.002⟩. ⟨hal-02061957⟩