中文摘要：
脓毒症中发生的不受控制的炎症会导致多器官损伤和休克，从而导致脓毒症患者死亡。然而，限制过度炎症的调节机制仍然难以捉摸。在这里，我们确定了一种称为信号淋巴细胞活化分子家族 7 （SLAMF7） 的 Ig 样受体是脓毒症期间炎症的关键抑制因子。我们发现脓毒症患者和脓毒症小鼠单核细胞/巨噬细胞上 SLAMF7 的表达显着升高。SLAMF7 通过与含有 Src 同源 2 的肌醇-5′-磷酸酶 1 （SHIP1） 合作，减弱巨噬细胞中 TLR 依赖性 MAPK 和 NF-κB 信号激活。此外，SLAMF7 与 SHIP1 和 TNF 受体相关因子 6 （TRAF6） 相互作用，抑制 TRAF6 的 K63 泛素化。此外，我们发现 SLAMF7 胞内结构域和 SHIP1 磷酸酶结构域内的酪氨酸磷酸化位点对于 SLAMF7、SHIP1 和 TRAF6 与 SLAMF7 介导的细胞因子产生的调节之间的相互作用是必需的。最后，我们证明 SLAMF7 通过下调巨噬细胞促炎细胞因子和抑制炎症诱导的器官损伤来预防致命的脓毒症和内毒素血症。综上所述，我们的研究结果揭示了 SLAMF7 在多种微生物脓毒症中的负调节作用，从而为脓毒症的治疗提供了视野。
英文摘要：
Uncontrolled inflammation occurred in sepsis results in multiple organ injuries and shock, which contributes to the death of patients with sepsis. However, the regulatory mechanisms that restrict excessive inflammation are still elusive. Here, we identified an Ig-like receptor called signaling lymphocyte activation molecular family 7 (SLAMF7) as a key suppressor of inflammation during sepsis. We found that the expression of SLAMF7 on monocytes/macrophages was significantly elevated in patients with sepsis and in septic mice. SLAMF7 attenuated TLR-dependent MAPK and NF-κB signaling activation in macrophages by cooperating with Src homology 2–containing inositol-5′‑phosphatase 1 (SHIP1). Furthermore, SLAMF7 interacted with SHIP1 and TNF receptor–associated factor 6 (TRAF6) to inhibit K63 ubiquitination of TRAF6. In addition, we found that tyrosine phosphorylation sites within the intracellular domain of SLAMF7 and the phosphatase domain of SHIP1 were indispensable for the interaction between SLAMF7, SHIP1, and TRAF6 and SLAMF7-mediated modulation of cytokine production. Finally, we demonstrated that SLAMF7 protected against lethal sepsis and endotoxemia by downregulating macrophage proinflammatory cytokines and suppressing inflammation-induced organ damage. Taken together, our findings reveal a negative regulatory role of SLAMF7 in polymicrobial sepsis, thus providing sights into the treatment of sepsis.
论文信息：
论文题目： HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis
期刊名称：J Clin Invest.
时间期卷：2023;133(6):e150224
在线时间：2023年2月7日
DOI：doi.org/10.1172/JCI150224.
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes and Control Liposomes
办事处：Target Technology（靶点科技）
Clodronate Liposomes氯膦酸盐脂质体助力LPS脓毒症模型SLAMF7 调节巨噬细胞炎症反应巨噬细胞研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于JCI：
LPS脓毒症模型SLAMF7 调节巨噬细胞炎症反应
Liposoma巨噬细胞清除剂ClodronateLiposomes氯膦酸二钠脂质体的材料和方法：
Macrophage depletion
Liposomes, composed of phospholipid bilayers and containing dichloromethylene diphosphonate (clodronate liposomes), or PBS (control liposomes) were purchased from Liposoma BV. A total of 100 μL clodronate-containing liposome suspension was injected i.p. into WT and SLAMF7-KO mice as previously described . Macrophages were depleted in the peritoneal lavage for up to 1 week after clodronate liposomes injection.
巨噬细胞清除/耗竭
脂质体由磷脂双层组成，含有二氯亚甲基二膦酸盐（氯膦酸盐脂质体）或 PBS（对照脂质体）购自荷兰Liposoma BV。如前所述，将总共 100 μL 含氯膦酸盐的脂质体悬浮液经腹腔注射到 WT 和 SLAMF7-KO 小鼠中。在注射氯膦酸盐脂质体后长达 1 周，巨噬细胞在腹腔灌洗液中耗尽。
