Imbalance between Th17 and Treg Cells May Play an Important Role in the Development of Chronic Unpredictable Mild Stress-Induced Depression in Mice
Imbalance between Th17 and Treg Cells May Play an Important Role in the Development of Chronic Unpredictable Mild Stress-Induced Depression in Mice
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Th17 和 Treg 细胞之间的不平衡可能在小鼠慢性不可预测的轻度应激性抑郁症的发展中发挥重要作用
DOI：
10.1159/000343100
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发表时间：
2013-01-01
影响因子：
2.4
通讯作者：
Wang, Ling-ling
中科院分区：
文献类型：
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作者：
Hong, Min;Zheng, Jie;Wang, Ling-ling
背景：最近的数据表明，重度抑郁症可能与细胞因子产生失调有关。然而，辅助性T细胞（Th）及其亚群在抑郁症的发展中的作用仍有待确定。本研究评估了小鼠模型抑郁症发展过程中Th细胞亚群和细胞因子的变化。方法：采用慢性不可预见性轻度应激（CHB）方法模拟小鼠抑郁行为。以旷场试验、蔗糖偏好、摄食量作为抑郁行为的评价指标。在CD 3S方案期间，在第3、7、14和21天，我们评估了行为变化、血清或刺激的（CD 3/CD 28）细胞培养基中的细胞因子水平、mRNA表达（ELISA、RT-PCR）、脾脏中的调节性T（Treg）和Th 17亚群（离体、流式细胞术、RT-PCR）以及CD 3/rIL-23刺激的Th 17细胞增殖（MTT测定）。结果如下：结果显示，在抑郁模型小鼠中，IL-4 mRNA表达和血清水平在第7天增加，而IFN-γ未观察到可检测的变化。值得注意的是，在后期观察到增殖能力降低的Th 17细胞比例降低，同时血清IL-23水平下降。相反，在中期观察到Treg细胞比例增加和Foxp 3 mRNA表达增加。相关分析表明，Tregs比例与蔗糖偏好呈负相关，而Th 17细胞增殖与蔗糖偏好呈显著正相关。此外，在血清中检测到增加的TGF-β水平，并且被认为是导致Th 17和Treg细胞之间失衡的关键因素。此外，与TGF-beta I型受体阻断小鼠相比，TGF-beta I型受体阻断小鼠的蔗糖偏好显著增加。结论：这些结果表明，在CNS诱导的抑郁症中，行为改变可能与Th 17和Treg细胞亚群之间的失衡密切相关，TGF-β可能是一种关键的调节细胞因子。版权所有（C）2012 S. Karger AG，巴塞尔
Background: Recent data suggest that major depression is potentially associated with dysregulated cytokine production. However, the roles of T helper (Th) cells and their subsets in the development of depression still remain to be determined. The present study assessed changes in Th cell subsets and cytokines during the development of depression in a mouse model. Methods: Chronic unpredictable mild stress (CUMS) was used to simulate depression behavior in mice. The open field test, sucrose preference, and ingestion were used as evaluative indicators of depressive behavior. During the CUMS protocol, on days 3, 7, 14, and 21, we assessed behavioral changes, cytokine levels in serum or stimulated (CD3/CD28) cell culture medium, and mRNA expression (ELISA, RT-PCR), regulatory T (Treg) and Th17 subsets in spleen (ex vivo, flow cytometry, RT-PCR), and CD3/rIL-23-stimulated Th17 cell proliferation (MTT assay). Results: The results showed that in the depression model mice, IL-4 mRNA expression and serum levels increased on day 7, while no detectable change was observed in IFN-gamma. Notably, a reduced proportion of Th17 cells with decreased proliferation capacity was observed at later stages, in parallel with a decline in serum IL-23 levels. In contrast, an increased Treg cell proportion and increased Foxp3 mRNA expression were observed in the mid-stages. Correlation analysis showed that the proportion of Tregs was correlated negatively with sucrose preference, while the proliferation of Th17 cells was notably correlated positively with sucrose preference. Also, an increased TGF-beta level was detected in serum and was believed to be a key factor responsible for the imbalance between Th17 and Treg cells. Furthermore, the sucrose preference in TGF-beta type I receptor blockade mice increased considerably, compared with CUMS mice. Conclusion: These results indicate that in CUMS-induced depression, behavioral changes may closely correlate with the imbalance between Th17 and Treg cell subsets, and TGF-beta may be a key regulatory cytokine. Copyright (C) 2012 S. Karger AG, Basel