Mesenchymal stem cells derived from human induced pluripotent stem cells modulate T-cell phenotypes in allergic rhinitis
Mesenchymal stem cells derived from human induced pluripotent stem cells modulate T-cell phenotypes in allergic rhinitis
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源自人类诱导多能干细胞的间充质干细胞调节过敏性鼻炎的 T 细胞表型
DOI：
10.1111/j.1398-9995.2012.02875.x
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发表时间：
2012-10-01
期刊：
影响因子：
12.4
通讯作者：
Xu, G.
中科院分区：
文献类型：
--
作者：
Fu, Q. L.;Chow, Y. Y.;Xu, G.
背景
人诱导多能干细胞（iPSCs）具有显著的自我更新能力以及分化为新型细胞类型（如间充质干细胞（MSCs））的潜能。iPSC - MSCs已被证明可促进组织再生并减轻组织缺血；然而，它们对Th2型偏倚的过敏性鼻炎（AR）和哮喘的免疫调节作用仍不清楚。
目的
本研究比较了iPSC - MSCs和骨髓来源的MSCs（BM - MSCs）对过敏性鼻炎患者外周血单个核细胞（PBMCs）中淋巴细胞增殖、T细胞表型以及细胞因子产生的免疫调节作用，并探究了iPSC - MSCs免疫调节特性的可能分子机制。
方法
在PBMCs与iPSC - MSCs或BM - MSCs的共培养中，使用3H - 胸腺嘧啶核苷（3H - TdR）摄取、羧基荧光素二乙酸琥珀酰亚胺酯（CFDA - SE）检测来评估淋巴细胞增殖；通过流式细胞术确定调节性T细胞（Treg）表型，并使用酶联免疫吸附测定法测量细胞因子水平。使用NS398和Transwell实验进一步评估两种MSCs的免疫调节特性。
结果
与BM - MSCs相似，我们确定iPSC - MSCs可显著抑制PBMCs中的淋巴细胞增殖并促进Treg反应（P < 0.05）。相应地，PBMCs上清液中的细胞因子环境（干扰素 - γ、白细胞介素 - 4、白细胞介素 - 5、白细胞介素 - 10和白细胞介素 - 13）发生了显著变化（P < 0.05）。iPSC - MSCs和BM - MSCs的免疫调节特性与前列腺素E2（PGE2）产生以及细胞 - 细胞接触有关。
结论
这些数据表明，iPSC - MSCs能够通过诱导Treg扩增来调节T细胞表型以抑制Th2，这提示iPSC - MSCs可作为成人MSCs的替代选择用于治疗过敏性气道疾病。
Background Human induced pluripotent stem cells (iPSCs) possess remarkable self-renewal capacity and the potential to differentiate into novel cell types, such as mesenchymal stem cells (MSCs). iPSC-MSCs have been shown to enhance tissue regeneration and attenuate tissue ischaemia; however, their contribution to the immune regulation of Th2-skewed allergic rhinitis (AR) and asthma remains unclear. Objective This study compared the immunomodulatory effects of iPSC-MSCs and bone marrow-derived MSCs (BM-MSCs) on lymphocyte proliferation, T-cell phenotypes and cytokine production in peripheral blood mononuclear cells (PBMCs) in patients with AR, and investigated the possible molecular mechanisms underlying the immunomodulatory properties of iPSC-MSCs. Methods In co-cultures of PBMCs with iPSC-MSCs or BM-MSCs, lymphocyte proliferation was evaluated using 3H-thymidine (3H-TdR) uptake, carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE) assays; the regulatory T-cell (Treg) phenotype was determined by flow cytometry, and cytokine levels were measured using an enzyme-linked immunosorbent assay. The immunomodulatory properties of both MSCs were further evaluated using NS398 and transwell experiments. Results Similar to BM-MSCs, we determined that iPSC-MSCs significantly inhibit lymphocyte proliferation and promote Treg response in PBMCs (P < 0.05). Accordingly, the cytokine milieu (IFN-?, IL-4, IL-5, IL-10 and IL-13) in the supernatants of PBMCs changed significantly (P < 0.05). The immunomodulatory properties of iPSC-MSCs and BM-MSCs were associated with prostaglandin E2 (PGE2) production and cellcell contact. Conclusions These data demonstrate that iPSC-MSCs are capable of modulating T-cell phenotypes towards Th2 suppression through inducing Treg expansion, suggesting that iPSC-MSCs can be used as an alternative candidate to adult MSCs to treat allergic airway diseases.