CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell content

© 2019 The Authors.
[Background]: Chronic hepatic inflammation leads to liver fibrosis, which may progress to cirrhosis, a condition with high morbidity. Our aim was to assess the as yet unknown role of innate immunity protein CD5L in liver fibrosis. [Methods]: CD5L was measured by ELISA in plasma samples from cirrhotic (n = 63) and hepatitis (n = 39) patients, and healthy controls (n = 7), by immunohistochemistry in cirrhotic tissue (n = 12), and by quantitative RT-PCR in mouse liver cell subsets isolated by cell sorting. Recombinant CD5L (rCD5L) was administered into a murine model of CCl4-induced fibrosis, and damage, fibrosis and hepatic immune cell infiltration, including the LyC6hi (pro-fibrotic)-LyC6low (pro-resolutive) monocyte ratio were determined. Moreover, rCD5L was added into primary human hepatic stellate cells to study transforming growth factor β (TGFβ) activation responses. [Findings]: Cirrhotic patients showed elevated plasma CD5L concentrations as compared to patients with hepatitis and healthy controls (Mann-Whitney test p
This work was supported by grants from the Fundació la Marató de TV3 (MTV3 2013-3610), AGAUR (2016 PROD 00094, 2017-SGR-490) to MRS, CSIC (PIE-201720E092) and also from the Instituto de Salud Carlos III (ISCIII), and ERDFs from the EU, ‘Una manera de hacer Europa’, (PI10/01565, PI13/1906, PI16/0974, PI13/02340, PI09/00751 and PI17/00673 to MRS, CA, and PS-B, respectively and PI14/00703 to LK). MRS, PS-B, CA, and CB were supported by the Miguel Servet (CPII14/00021; CPII15/00041), Ramón y Cajal (RYC-2010-07249), and Juan de la Cierva (FJCI-2014-20,505) programs, respectively.