Sorting nexin 10 acting as a novel regulator of macrophage polarization mediates inflammatory response in experimental mouse colitis.
Sorting nexin 10 acting as a novel regulator of macrophage polarization mediates inflammatory response in experimental mouse colitis.
复制标题
分选 nexin 10 作为巨噬细胞极化的新型调节剂介导实验性小鼠结肠炎的炎症反应
DOI：
10.1038/srep20630
复制
发表时间：
2016-02-09
影响因子：
4.6
通讯作者：
Shen X
中科院分区：
文献类型：
--
作者：
You Y;Zhou C;Li D;Cao ZL;Shen W;Li WZ;Zhang S;Hu B;Shen X
巨噬细胞响应微环境的变化，分化成功能不同的表型，在炎症性肠病（IBD）的发病机制中起着至关重要的作用。在这里，我们研究了分选连接蛋白10（SNX 10），一种参与内体运输和破骨细胞成熟的蛋白质，对巨噬细胞极化和小鼠结肠炎进展的调节的影响。我们的研究结果表明，SNX 10缺陷增加了M2型单核细胞/巨噬细胞的数量，并保护免受葡聚糖硫酸钠（DSS）诱导的结肠炎症和病理损伤。在体外研究中，我们发现SNX 10的缺陷使来自小鼠骨髓或人外周血单核细胞（PBMC）的巨噬细胞向抗炎M2表型极化，这被SNX 10质粒转染部分逆转。SNX 10 −/−巨噬细胞的连续转移改善了WT小鼠的结肠炎。然而，WT巨噬细胞的转移加重了SNX 10 −/−小鼠的结肠炎。我们的数据揭示了SNX 10在巨噬细胞极化中的关键作用和新功能。SNX 10功能的丧失可能是IBD的一种潜在的有希望的治疗策略。
In response to changes in microenvironment, macrophages polarize into functionally distinct phenotypes, playing a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Here, we investigated the effects of sorting nexin 10 (SNX10), a protein involved in endosomal trafficking and osteoclast maturation, on regulation of macrophage polarization and progression of mouse colitis. Our results revealed that SNX10 deficiency increased the population of M2-type monocytes/macrophages and protected against colonic inflammation and pathological damage induced by dextran sulfate sodium (DSS). Byin vitrostudy, we showed that deficiency of SNX10 polarized macrophages derived from mouse bone marrow or human peripheral blood mononuclear cells (PBMCs) towards an anti-inflammatory M2 phenotype, which partially reversed by SNX10 plasmid transfection. Adoptive transfer of SNX10−/−macrophages ameliorated colitis in WT mice. However, transfer of WT macrophages exacerbated colitis in SNX10−/−mice. Our data disclose a crucial role and novel function for SNX10 in macrophage polarization. Loss of SNX10 function may be a potential promising therapeutic strategy for IBD.