Characterizing Kupffer Cell Production of CD5 Antigen-Like and Its Function on Regulating Migration of Natural Killer T Cells

CD5 antigen-like (CD5L) is a multifunctional glycoprotein characterized for its role in the lipid metabolism, particularly within macrophages. In the liver, CD5L strongly correlates with liver injury. This study explored the role of CD5L on liver lipid accumulation and inflammatory response. CD5L promoted lipid uptake in hepatocytes and stellate cells. In multiple models of liver injury, expression of Cd5l was associated with that of Clec4f, a marker for liver macrophages, consistent with its role as a macrophage survival factor. Transwell assay was used to demonstrate a novel function of CD5L on promoting migration of natural killer T cells. This effect was independent of CD36, the characterized receptor of CD5L. This effect was also observed with liver macrophages, which are the cellular source for CD5L, and blocking CD5L attenuated natural killer T cell migration induced by liver macrophages. Finally, plasma levels of CD5L correlated with poor patient response to immune check point therapy that is dependent on response of T-cell populations. In addition, plasma CD5L levels correlated with levels of steatosis and severity of steatotic liver injury. Given the association between liver steatosis and poor response to immune checkpoint therapy, these data suggest that plasma CD5L levels may serve as a predictive biomarker for patient response to immune checkpoint therapy.