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

LECT2(白细胞衍生趋化素2)最初被鉴定为可能在体外对人中性粒细胞具有趋化活性。它是一种16 kDa的蛋白质，在肝脏中优先表达。它的同源物已经在许多脊椎动物中被广泛发现。目前的证据表明，LECT2可能是一种类似细胞因子的多功能蛋白质。然而，LECT2在体内的功能仍不清楚。为了阐明这种蛋白质在体内的作用，我们产生了LECT2缺陷(LECT2^&lt；-/-&gt；)小鼠。我们发现，在LECT2^-lt；-/-&gt；小鼠肝脏中自然杀伤T(NKT)细胞的比例显著增加，尽管传统T细胞、NK细胞和其他细胞类型的比例与野生型小鼠相似。与肝脏NKT细胞数量增加一致的是，在α-半乳糖神经酰胺(α-GalCer)刺激下，LECT2^-lt；-/-&GT；小鼠IL-4和干扰素-γ的产生增加，这种刺激特异性地激活Vα14^+NKT细胞。此外，在体外培养的小鼠肝单个核细胞中，NKT细胞介导的对同基因胸腺细胞的细胞毒活性也增加。有趣的是，在使用刀豆蛋白A治疗后，LECT2^&lt；-/-&gt；小鼠的肝损伤加重，可能是因为IL-4和Fas配体的表达显著增加。这些结果提示，LECT2可能调节肝脏NKT细胞的动态平衡，并可能参与肝炎的发病机制。

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.