Study on function of cytokine LECT2 expressed in the liver using a mouse

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LECT2 (leukocyte cell-derived chemotaxin 2) was originally identified for its possible chemotactic activity against human neutrophils in vitro. It is a 16-kDa protein that is preferentially expressed in the liver. Its homologues have been widely identified in many vertebrates. Current evidence suggests that LECT2 may be a multifunctional protein like cytokines. However, the function of LECT2 in vivo remains unclear. To elucidate the role of this protein in vivo, we have generated LECT2-deficient (LECT2^<-/->) mice. We found that the proportion of natural killer T (NKT) cells in the liver increased significantly in LECT2^<-/-> mice, although those of conventional T cells, NK cells, and other cell types were comparable with those in wild-type mice. Consistent with increased hepatic NKT cell number, production of IL-4 and IFN-_Y was augmented in LECT2^<-/-> mice upon stimulation with α-galactosylceramide (α-GalCer), which specifically activates Vα14^+ NKT cells. In addition, NKT cell-mediated cytotoxic activity against syngeneic thymocytes also increased in hepatic mononuclear cells obtained from LECT2^<-/-> mice in vitro. Interestingly, the hepatic injury was exacerbated in LECT2^<-/-> mice upon treatment with Con A, possibly because of the significantly higher expression of IL-4 and Fas ligand. These results suggest that LECT2 might regulate the homeostasis of NKT cells in the liver, and might be involved in the pathogenesis of hepatitis.