The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair.

中文翻译：

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胱硫醚γ裂解酶 (Cth) 通过 ERK1/2 诱导巨噬细胞胞吞作用，从而调节肠道屏障修复

肠道缺血再灌注损伤（I/R）引起的炎症反应与危重患者感染并发症和死亡密切相关，及时有效清除凋亡细胞是减轻炎症反应的重要环节。研究表明吞噬细胞的胞吞作用起着重要作用。最近，利用小肠类器官模型的研究表明，巨噬细胞胞吞作用可以促进肠上皮的修复能力。然而，尚无研究报道胞吞作用在动物模型中 I/R 修复中的作用。我们使用体内胞吞作用测定，发现巨噬细胞胞吞作用在缺血再灌注后修复和维持肠道屏障功能中发挥着不可或缺的作用。此外，诱导巨噬细胞胞吞作用的具体分子机制是Cth-ERK1/2依赖性的。我们发现 Cth 在体内和体外驱动巨噬细胞胞吞作用。过表达/沉默 Cth 分别促进/抑制 ERK1/2 通路，进而影响胞吐作用并介导肠道屏障恢复。此外，我们发现临床患者Cth和巨噬细胞胞吞作用的水平与肠道功能的恢复呈正相关。Cth可激活ERK1/2信号通路，诱导巨噬细胞胞吞作用，从而促进肠道屏障修复。