The problem

Chronic liver disease causes high morbidity and mortality worldwide. The liver deals with blood microorganisms and damage-associated molecular patterns (DAMPs) released from injured organs, thus performing vital immune, metabolic and clearance functions that require the uptake of nutrients and toxins. Innate immunity receptors and cells, specially macrophages, are key players in the response to these threats. However, their unbalanced expression and uncontrolled responses can worsen the prognosis of liver disease. It is well known that continuous liver inflammation leads to hepatic fibrosis, which frequently brings about cirrhosis and ultimately hepatocellular carcinoma.

The approach

Our aim is to define the role of innate immune proteins as prognostic or diagnostic biomarkers of disease. We also aim at generating knowledge for the development of new pharmacological agents that modulate macrophage responses. In this context, our interests are at present mostly centered on the role of the macrophage protein CD5L in the control of immune homeostasis and inflammatory disease.

Main discoveries and innovations

• CD5L is a critical regulator of inflammation by inducing macrophage polarization to an immunosuppressive phenotype through the activation of autophagy
• CD5L is a key player in liver fibrogenesis
• In acute-on-chronic liver failure, alteration of circulating plasma extracellular vesicle content with a loss of anti-inflammatory (CD5L) and pro-resolving (RvE1) molecules involved in the control of acute inflammation