Induced pluripotent stem cell-derived mesenchymal stem cells activate quiescent T cells and elevate regulatory T cell response via NF-κB in allergic rhinitis patients.
Induced pluripotent stem cell-derived mesenchymal stem cells activate quiescent T cells and elevate regulatory T cell response via NF-κB in allergic rhinitis patients.
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诱导多能干细胞衍生的间充质干细胞在过敏性鼻炎患者中激活静止 T 细胞并通过 NF-κ B 提高调节性 T 细胞反应
DOI：
10.1186/s13287-018-0896-z
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发表时间：
2018-06-19
影响因子：
7.5
通讯作者：
Fu QL
中科院分区：
文献类型：
--
作者：
Fan XL;Zeng QX;Li X;Li CL;Xu ZB;Deng XQ;Shi J;Chen D;Zheng SG;Fu QL
先前已经证明，诱导多能干细胞（iPSC）衍生的间充质干细胞（MSC）对活化的T细胞具有免疫抑制作用。然而，iPSC-MSC对静止T细胞的影响仍然未知。本研究的目的是确定iPSC-MSC对来自变应性鼻炎（AR）患者的静息外周血单个核细胞（PBMC）的免疫调节作用。在没有任何刺激的情况下将PBMC与iPSC-MSC共培养，随后分析淋巴细胞增殖、T细胞活化、TH 1/TH 2和调节性T（Treg）细胞分化以及Treg细胞功能。可溶性因子和细胞-细胞接触的作用进行了检查，以调查所涉及的机制。iPSC-MSC促进静息淋巴细胞的增殖，活化CD 4+和CD 8 + T细胞，并且在没有任何额外刺激的情况下上调和活化Treg细胞。此外，iPSC-MSC平衡了偏向的TH 1/TH 2细胞因子水平。细胞-细胞接触被证实是一个可能的机制。NF-κB在iPSC-MSCs对静止T细胞的免疫调节作用中起重要作用。iPSC-MSC激活静止T细胞并提高AR患者中的调节性T细胞应答，表明iPSC-MSC根据疾病的阶段具有不同的免疫调节功能。因此，iPSC-MSC是治疗过敏性气道炎症的潜在治疗候选者。本文的在线版本（10.1186/s13287-018-0896-z）包含补充材料，可供授权用户使用。
It has been demonstrated previously that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs) have immunosuppressive effects on activated T cells. However, the effects of iPSC-MSCs on quiescent T cells are still unknown. The aim of this study was to identify the immunomodulatory role of iPSC-MSCs on resting peripheral blood mononuclear cells (PBMCs) from allergic rhinitis (AR) patients. PBMCs were cocultured with iPSC-MSCs without any stimulation, following which lymphocyte proliferation, activation of T cells, TH1/TH2 and regulatory T (Treg) cell differentiation, and Treg cell function were analyzed. The roles of soluble factors and cell–cell contact were examined to investigate the mechanisms involved. iPSC-MSCs promoted the proliferation of resting lymphocytes, activated CD4+ and CD8+ T cells, and upregulated and activated Treg cells without any additional stimulation. In addition, iPSC-MSCs balanced biased TH1/TH2 cytokine levels. Cell–cell contact was confirmed to be a possible mechanism involved. NF-κB was identified to play an important role in the immunomodulatory effects of iPSC-MSCs on quiescent T cells. iPSC-MSCs activate quiescent T cells and elevate regulatory T-cell response in AR patients, suggesting different immunomodulatory functions of iPSC-MSCs according to the phases of diseases. Therefore, iPSC-MSCs are a potential therapeutic candidate for treating allergic airway inflammation. The online version of this article (10.1186/s13287-018-0896-z) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
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影响因子：
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