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网页传奇制作-研究发现间充质干细胞治疗自身免疫性疾病新机制

作者:超变单职业_变态单职业_超变单职业传奇_就来新开单职业传奇发布网2019-07-11 16:23类型:刚开一秒传奇Sf 已有104人围观

2019年6月,在传奇SF的游戏中,国际学术期刊Cell Metabolism发表了中国科学院上海营养与健康研究所时玉舫/王莹课题组的最新研究成果。在该项研究中,研究人员系统分析了低氧条件下间充质干细胞(Mesenchymal Stem Cells, MSCs)的蛋白表达谱,发现其分泌的胰岛素样生长因子-2(Insulin like growth factor-2, IGF-2)是治疗自身免疫性疾病的重要分子,并揭示了IGF2执行免疫抑制功能的分子机制及其在对抗自身免疫性疾病中的应用潜能。

在研究间充质干细胞对实验性自身免疫性脑脊髓炎(EAE)的影响时,研究组发现胰岛素样生长因子2 (IGF-2)在训练巨噬细胞在其成熟过程中成为抗炎细胞方面发挥了关键作用。IGF-2通过预先编程使成熟巨噬细胞参与氧化磷酸化(OXPHOS)而发挥其作用。IGF-2预编程巨噬细胞即使在促炎刺激下也能维持线粒体复合物V的活性,从而使程序性死亡配体1 (PD-L1)表达升高。PD-L1中和消除了IGF-2对EAE的有益作用。此外,将IGF -2预编程巨噬细胞过继转移到EAE小鼠可增加treg,减轻疾病。他们的结果表明,IGF-2对巨噬细胞的反应性的塑造对炎症性疾病的管理是有效的,并且OXPHOS可以预先确定巨噬细胞的抗炎性。

最近的研究表明,巨噬细胞可以通过改变反应性来训练,通过向这些细胞传授抗炎能力来提高对抗自身免疫性疾病的可能性。

附:英文原文

Title: IGF-2 Preprograms Maturing Macrophages to Acquire Oxidative Phosphorylation-Dependent Anti-inflammatory Properties

Author: Liming Du, Liangyu Lin, Qing Li, Changshun Shao, Ying Wang, Yufang Shi

Issue&Volume:Jun 04, 2019 Volume 29Issue 6

Abstract: Recent investigations revealed that macrophages could be trained with an altered responsiveness, raising the possibility of combating autoimmune diseases by imparting anti-inflammatory capabilities to these cells. While investigating the effect of mesenchymal stem cells on experimental autoimmune encephalomyelitis (EAE), we found a critical role of insulin-like growth factor 2 (IGF-2) in training macrophages to become anti-inflammatory during their maturation. IGF-2 exerts its effects by preprogramming maturing macrophages to commit oxidative phosphorylation (OXPHOS). IGF-2-preprogrammed macrophages maintained the mitochondrial complex V activities even upon pro-inflammation stimulation, thus enabling an elevated programmed death-ligand 1 (PD-L1) expression. PD-L1 neutralization abolished the beneficial effect of IGF-2 on EAE. Furthermore, adoptive transfer of IGF-2-preprogrammed macrophages to EAE mice increased Tregs and alleviated the diseases. Our results demonstrate that shaping macrophage responsiveness by IGF-2 is effective in managing inflammatory diseases, and the OXPHOS commitment can be preset to determine the anti-inflammatory fate of macrophages.

DOI: https://doi.org/10.1016/j.cmet.2019.01.006

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30006-3

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新if:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx

-Jun 04, 2019 Volume 29Issue 6

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