Trovato FM, Zia R, Napoli S, et al. - In the present study, the researchers sought to describe the lysophosphatidylcholine (LPC)-autotaxin (ATX)-lysophosphatidic acid (LPA) axis and mechanistically evaluate its role on innate immune dysfunction in patients with acute-on-chronic liver failure (ACLF). Three hundred forty-two individuals were selected and characterized for blood lipid, cytokines, phospholipase, and ATX concentration. Peripheral blood mononuclear cells and CD14 ^{+ monocytes were cultured with LPC, or its ATX-derived product, LPA, with or without lipopolysaccharide stimulation and evaluated for surface marker phenotype, cytokines production, ATX, and LPA-receptor expression, and phagocytosis. Patients with high-grade ACLF had the lowest LPC concentrations, which increased over the first 3 days of admission. ATX up-regulation in ACLF encourages LPA production from LPC. LPA suppresses MerTK/CD163 expression while increasing monocyte proinflammatory cytokine production. This metabolic pathway could be studied to see if it can be used to therapeutically reprogram monocytes in ACLF.}