In line, therapeutic administration of this antibody in experimental chronic metabolic injury attenuated hepatic macrophage infiltration, pro-inflammatory cytokine levels and steatosis development in mice. On the one hand, our experiments using aCXCL16 revealed that blocking this chemokine pathway almost completely abolished the rapid accumulation of hepatic NKT cells in response to an acute injury. This is well in line with a prior in vitro experiment from our group, demonstrating that CXCR6 is specifically required by NKT, but not other CXCR6-expressing lymphocytes, to migrate towards CXCL16. Moreover, it had been reported that CXCL16 neutralization reduced accumulation of mature NK1.1+, but not immature NK1.12 NKT cell recent thymic emigrants in the liver in homeostatic conditions in vivo. NKT cells display a unique population of unconventional T cells that express both a T cell receptor and NK1.1 receptor from NK cells. There are different types of NKT cell subsets that are defined by the ability of recognizing a-galactosylceramide presented by the non-classical MHC-like molecule CD1d, termed type-I classical, type-II non classical and CD1d-independent NK1.1+ NKT cells. Especially the type-I NKT cells, which the by far largest subset in the liver, have the ability to secrete various types of cytokines within a very short time period after activation, including IL-4 and IFNc. In line, mice that are deficient for the CXCL16 chemokine displayed a reduced number of liver NKT cells, decreased production of IFNc and IL-4 by administration of a-GalCeramide and impaired inflammatory responses against Propionibacterium MK-1775 acnes-infections in vivo. On the other hand, our experiments indicate that aCXCL16 could be an interesting therapeutic strategy in hepatic inflammation and steatohepatitis. Importantly, the same aCXCL16 antibody had been tested as an interventional approach for severe inflammatory conditions before. In a murine immunological liver injury induced by Bacille Calmette-Guerin and lipopolysaccharide, mice treated with aCXCL16 showed reduced liver injury, inflammation and improved survival. Administration of aCXCL16 also reduced colonic inflammation in mouse models of on dextran sodium sulfate- and trinitrobenzene sulfonic acidinduced colitis. In our hands, therapeutic administration of aCXCL16 during the last three weeks of a 6-weeks course of MCD diet in mice significantly reduced the number of hepatic macrophages, alongside minor reductions in intrahepatic levels of pro-inflammatory cytokines, and steatosis development. The link between macrophages and progression of fatty liver degeneration is well established, as macrophages release many inflammatory mediators that not only attract additional immune cells, but also drive oxidative stress and intrahepatocytic lipid accumulation. Our experiments now indicate that blocking CXCL16 effectively reduces pro-inflammatory macrophages in experimental steatohepatitis.