类器官transplantation通过L-苹果酸介导的M2型巨噬细胞极化减轻小鼠肠道缺血/再灌注损伤

中文摘要：

肠道类器官transplantation是一种治疗黏膜损伤的有前景的疗法。然而，移植的类器官如何调节受体小鼠的免疫微环境，以及它们在治疗肠道缺血-再灌注（I/R）损伤中的作用仍然不清楚。在这里，我们建立了一种将肠道类器官transplantation到肠道I/R小鼠的方法。我们发现移植能够改善小鼠的生存率，促进肠道干细胞的自我更新，并调节肠道I/R后的免疫微环境，这取决于巨噬细胞极化为抗炎性M2表型的增强能力。具体来说，我们报告L-苹果酸（MA）在移植小鼠的类器官衍生条件培养基和盲肠内容物中表达量高且富集，证明类器官在移植过程中分泌MA。体内和体外实验都表明，MA诱导M2巨噬细胞极化，并以SOCS2依赖的方式恢复白细胞介素-10水平。这项研究为肠道I/R损伤提供了一种治疗策略。

英文摘要：

Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how the transplanted organoids regulate the immune microenvironment of recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish a method for transplanting intestinal organoids into intestinal I/R mice. We find that transplantation improve mouse survival, promote self-renewal of intestinal stem cells and regulate the immune microenvironment after intestinal I/R, depending on the enhanced ability of macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, we report that L-Malic acid (MA) is highly expressed and enriched in the organoids-derived conditioned medium and cecal contents of transplanted mice, demonstrating that organoids secrete MA during engraftment. Both in vivo and in vitro experiments demonstrate that MA induces M2 macrophage polarization and restores interleukin-10 levels in a SOCS2-dependent manner. This study provides a therapeutic strategy for intestinal I/R injury.

论文信息：

论文题目：Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization

期刊名称：Nature Communications

时间期卷：14, Article number: 6779 (2023)

在线时间：2023年10月25日

DOI：doi.org/10.1038/s41467-023-42502-0

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氯膦酸盐脂质体清除肠道巨噬细胞，在肠道缺血再灌注的炎性模型中单核巨噬细胞功能研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：类器官transplantation通过L-苹果酸介导的M2型巨噬细胞极化减轻小鼠肠道缺血/再灌注损伤

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：

Depletion of intestinal macrophages

Two hundred microliters of clodronate- or PBS-loaded liposomes (CP-005-005, LIPOSOMA, Groningen, The Netherlands) were intravenously injected into mice thrice on alternating days prior to intestinal I/R to deplete intestinal macrophages.

材料和方法文献截图：