Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe concanavalin A-induced hepatitis
Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe concanavalin A-induced hepatitis
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DOI：
10.4049/jimmunol.173.1.579
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发表时间：
2004-07-01
影响因子：
4.4
通讯作者：
Yamagoe, S
中科院分区：
文献类型：
--
作者：
Saito, T;Okumura, A;Yamagoe, S
白细胞细胞源趋化因子2（LECT 2）最初被鉴定为可能的体外对人中性粒细胞的趋化活性。它是一种16 kDa的蛋白质，优先在肝脏中表达。它的同源物在许多脊椎动物中被广泛鉴定。目前的证据表明，LECT 2可能是一种多功能蛋白质，如细胞因子。然而，LECT 2在体内的功能仍不清楚。为了阐明这种蛋白在体内的作用，我们已经产生了LECT 2缺陷（LECT 2（-/-））小鼠。我们发现，在LECT 2（-/-）小鼠中，肝脏中NKT细胞的比例显著增加，尽管常规T细胞、NK细胞和其他细胞类型的比例与野生型小鼠相当。与肝NKT细胞数量增加一致，在用α-半乳糖神经酰胺刺激后，LECT 2（-/-）小鼠中IL-4和IFN-γ的产生增加，所述α-半乳糖神经酰胺特异性激活Valpha 14 NKT细胞。此外，NKT细胞介导的对同系胸腺细胞的细胞毒活性在体外从LECT 2（-/-）小鼠获得的肝单核细胞中增加。有趣的是，LECT 2（-/-）小鼠在用Con A治疗后肝损伤加重，这可能是因为IL-4和Fas配体的显著更高表达。这些结果表明，LECT 2可能调节肝脏中NKT细胞的稳态，并可能参与肝炎的发病机制。
Leukocyte cell-derived chemotaxin 2 (LECT2) 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 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, the production of IL-4 and IFN-gamma was augmented in LECT2(-/-) mice upon stimulation with a-galactosylceramide, which specifically activates Valpha14 NKT cells. In addition, NKT cell-mediated cytotoxic activity against syngeneic thymocytes 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.