Hemorrhagic shock (HS) leads to intestinal damage and subsequent multiple organ dysfunction syndrome. Intestinal barrier dysfunction is the main cause of multiple organ failure associated with HS. Leukocyte immunoglobulin-like receptor B4 (Lilrb4) belongs to the Ig superfamily and is a vital natural immunomodulatory receptor. The purpose of this study was to identify the role and molecular mechanism of Lilrb4 in HS-induced ileal injury. In this work, HS was established by femoral artery cannula and 90 min of HS (blood pressure, 35–40 mmHg), followed by resuscitation. RNA sequencing analysis showed that Lilrb4 was highly expressed in the ileum of HS rats. As observed, HS rats exhibited severe ileal injury, characterized by enlarged subepithelial space, edema, exfoliation and extensive loss of villi. Whereas, lentivirus system-mediated Lilrb4 overexpression considerably mitigated these alterations. HS led to increased release of markers associated with intestinal injury, which was effectively reversed by Lilrb4 overexpression. In addition, after resuscitation, Lilrb4 overexpression inhibited HS-triggered inflammatory response, as evidenced by decreased levels of proinflammatory cytokines. Lilrb4 also inhibited the activation of NF-κB signal induced by HS. Notably, Lilrb4 modulated the balance of regulatory T (Treg)-T helper 17 (Th17) cells in the mesenteric lymph node (MLN), which may also contribute to its protective role in HS progression. In aggregate, these findings confirmed that Lilrb4 overexpression protected against ileal injury caused by HS, indicating that Lilrb4 may be a potential candidate for the treatment of HS.

中文翻译：

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Lilrb4改善失血性休克大鼠回肠损伤并抑制NF-κB信号通路的激活

失血性休克（HS）会导致肠道损伤和随后的多器官功能障碍综合征。肠屏障功能障碍是热射病相关多器官功能衰竭的主要原因。白细胞免疫球蛋白样受体 B4 (Lilrb4) 属于 Ig 超家族，是一种重要的天然免疫调节受体。本研究的目的是确定 Lilrb4 在 HS 诱导的回肠损伤中的作用和分子机制。在这项工作中，通过股动脉插管和 90 分钟的 HS（血压，35-40 mmHg）建立 HS，然后进行复苏。RNA测序分析显示Lilrb4在HS大鼠回肠中高表达。据观察，HS大鼠表现出严重的回肠损伤，其特征是上皮下间隙扩大、水肿、剥脱和绒毛广泛损失。然而，慢病毒系统介导的 Lilrb4 过度表达大大减轻了这些改变。HS 导致与肠道损伤相关的标记物释放增加，Lilrb4 过表达可有效逆转这种情况。此外，复苏后，Lilrb4 过表达抑制 HS 触发的炎症反应，促炎细胞因子水平下降就证明了这一点。Lilrb4 还抑制 HS 诱导的 NF-κB 信号激活。值得注意的是，Lilrb4 调节肠系膜淋巴结 (MLN) 中调节性 T (Treg)-T 辅助 17 (Th17) 细胞的平衡，这也可能有助于其在 HS 进展中的保护作用。总的来说，这些发现证实了 Lilrb4 过度表达可以防止 HS 引起的回肠损伤，表明 Lilrb4 可能是治疗 HS 的潜在候选者。