Laboratory of Biochemistry and Molecular Biology, Ningbo University, Ningbo 315211, China.
J Exp Med. 2013 Jan 14;210(1):5-13. doi: 10.1084/jem.20121466. Epub 2012 Dec 17.
Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine and reduced plasma levels were found in patients with sepsis. However, precise functions and mechanisms of LECT2 remain unclear. The aim of the present study was to determine the role of LECT2 in modulating immune responses using mouse sepsis models. We found that LECT2 treatment improved outcome in mice with bacterial sepsis. Macrophages (MΦ), but not polymorphonuclear neutrophils, mediated the beneficial effect of LECT2 on bacterial sepsis. LECT2 treatment could alter gene expression and enhance phagocytosis and bacterial killing of MΦ in vitro. CD209a was identified to specifically interact with LECT2 and mediate LECT2-induced MΦ activation. CD209a-expressing MΦ was further confirmed to mediate the effect of LECT2 on sepsis in vivo. Our data demonstrate that LECT2 improves protective immunity in bacterial sepsis, possibly as a result of enhanced MΦ functions via the CD209a receptor. The modulation of MΦ functions by LECT2 may serve as a novel potential treatment for sepsis.
白细胞细胞来源的趋化因子 2 (LECT2) 是一种多功能细胞因子，败血症患者的血浆水平降低。然而，LECT2 的精确功能和机制仍不清楚。本研究旨在使用小鼠败血症模型确定 LECT2 在调节免疫反应中的作用。我们发现 LECT2 治疗可改善细菌性败血症小鼠的预后。巨噬细胞 (MΦ)，而不是多形核白细胞，介导 LECT2 对细菌性败血症的有益作用。LECT2 治疗可改变基因表达并增强体外 MΦ的吞噬作用和细菌杀伤作用。鉴定出 CD209a 特异性与 LECT2 相互作用并介导 LECT2 诱导的 MΦ 激活。进一步证实表达 CD209a 的 MΦ 介导 LECT2 对体内败血症的作用。我们的数据表明，LECT2 可改善细菌性败血症的保护性免疫，可能是通过 CD209a 受体增强 MΦ 功能的结果。LECT2 对 MΦ 功能的调节可能成为败血症的一种新的潜在治疗方法。
