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BBI:时玉舫等发现间充质干细胞在应激过程中保护免疫细胞

  1. BBI
  2. 免疫细胞
  3. 应激
  4. 时玉舫
  5. 间充质干细胞

来源:上海生命科学研究院 2014-04-11 20:24

近日,国际学术期刊Brain,Behavior,and Immunity 在线发表了中国科学院上海生命科学研究院健康科学研究所时玉舫研究组题为Mesenchymal Stem Cells Prevent Restraint Stress-Induced Lymphocyte Depletion via Int

近日,国际学术期刊Brain,Behavior,and Immunity 在线发表了中国科学院上海生命科学研究院健康科学研究所时玉舫研究组题为Mesenchymal Stem Cells Prevent Restraint Stress-Induced Lymphocyte Depletion via Interleukin-4 的研究论文,报道了间充质干细胞(mesenchymal stem cells, MSCs)能够抵抗机体应激引起的淋巴细胞数量剧烈减少及其相关机制。

慢性压力应激(chronic stress)会引起免疫系统功能紊乱,在多种免疫紊乱性疾病的发生、发展过程中起重要作用,如癌症、自身免疫性疾病、感染等。

然而,目前仍缺乏有效制约长期身心压力对健康影响的对抗措施(countermeasures)。模拟慢性身心压力的一个较好的动物模型是束缚应激(Restraint Stress, RS)。它主要通过激活小鼠的下丘脑-垂体-肾上腺轴(Hypothalamic-Pituitary-Adrenal axis),使其分泌大量糖皮质激素和内啡肽,引起淋巴细胞凋亡,促进淋巴细胞数量大幅减少。最近,众多基础及临床研究已经表明间充质干细胞(MSCs)具有显著的调节免疫系统的作用,然而由于研究体系的缺乏,目前尚未对MSCs是否能调节应激相关的免疫紊乱进行系统研究。博士研究生曹刚等利用RS实验系统,发现给予小鼠注射MSCs可以有效地预防淋巴细胞数量减少。它的保护效果不是通过调节循环系统中激素的水平实现的,而是直接对抗激素诱导淋巴细胞凋亡。通过体外凋亡保护实验筛选候选分子,研究者发现介导MSCs保护功能的可能是白介素-4(interleukin-4, IL-4)。当在RS小鼠模型中阻断IL-4时,研究发现MSCs对RS诱导淋巴细胞数量减少的保护作用被抑制。此外,应用STAT6缺陷小鼠进一步验证IL-4及其信号通路调控在介导MSCs对RS诱导淋巴细胞减少保护功能中的重要作用。与此同时,研究者还发现给予RS小鼠注射MSCs能促进淋巴细胞产生更多的IL-4。总之,本研究揭示了MSCs能有效预防RS诱导的淋巴细胞减少,而且这种保护作用主要依赖于IL-4。该研究为应用此类干细胞预防慢性身心压力引起的免疫功能紊乱提供了实验基础和理论依据。

该研究得到了国家科技部、中国科学院战略性先导科技专项、国家自然科学基金委及上海市科委等的资助。(生物谷Bioon.com)

生物谷推荐的英文摘要:

Brain,Behavior,and Immunity   doi:10.1016/j.bbi.2014.01.013

Mesenchymal stem cells prevent restraint stress-induced lymphocyte depletion via interleukin-4

Gang Caoa, Qian Yanga, Siyu Zhanga, Chunliang Xua, Arthur I. Robertsb, Ying Wanga, Yufang Shia, b

Chronic stress has dramatic impacts on the immune system and consequently contributes to the onset and progression of a variety of diseases, including cancer, immune disorders, and infections. Recent studies in animals and humans have demonstrated that mesenchymal stem cells (MSCs) significantly modulate the immune system. Here we show that administration of MSCs in vivo prevents lymphocyte depletion induced by physical restraint stress (12:12-h stress–rest, 2 repetitions) in mice. This effect was found to be exerted not through modulation of glucocorticoid levels in the circulation, but rather through direct effects on lymphocyte apoptosis. By testing various possible protective mechanisms, we found that IL-4 provides a strong anti-apoptosis signal to lymphocytes in the presence of dexamethasone. When neutralizing antibody against IL-4 was co-administered with MSCs to restraint-stressed mice, the protective effect of MSCs was diminished. Furthermore, in mice deficient in STAT6, a key molecule in IL-4 receptor-mediated signaling, MSCs had no effect on restraint stress-induced lymphocyte depletion. Additionally, MSCs administered to stressed mice promoted IL-4 production by splenocytes. This study reveals that MSCs can effectively prevent stress-induced lymphocyte apoptosis in an IL-4-dependent manner and provides novel information for the development of countermeasures against the deleterious effects of stress on the immune system.

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