Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells
Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells
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DOI：
10.4049/jimmunol.179.3.1595
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发表时间：
2007-08-01
影响因子：
4.4
通讯作者：
Collin, Matthew P.
中科院分区：
文献类型：
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作者：
Haniffa, Muzlifah A.;Wang, Xiao-Nong;Collin, Matthew P.
骨髓间充质干细胞（MSC）具有有效的免疫抑制特性，并已被提倡用于人类治疗。人们对它们的抑制能力的性质知之甚少，但据说这是一种原始的干细胞功能。证明成纤维细胞 (Fb) 等成体基质细胞可以调节 T 细胞将对免疫调节和细胞治疗产生重要影响。在本报告中，我们表明真皮 Fb 通过自体皮肤 APC 和其他刺激物抑制同种异体 T 细胞活化。 Fb 通过可溶性因子介导抑制，但这严重依赖于活化 T 细胞的 IFN-γ。 IFN-γ 会诱导 Fb 中的 IDO，而加速的色氨酸代谢至少在一定程度上是抑制 T 细胞增殖的原因。 T 细胞抑制是可逆的，在激活过程中短暂暴露于 Fb 会重新编程 T 细胞，在重新刺激时增加 IL-4 和 IL-10 的分泌。基质细胞增加的 Th2 极化与移植物抗宿主病人类模型病理变化的改善相关。真皮 Fb 在体外具有高度克隆形成性，表明 Fb 介导的免疫抑制并非由于罕见 MSC 的生长所致，尽管真皮 Fb 仍然难以通过表型或转分化能力与 MSC 区分开。这些结果表明，免疫抑制是基质细胞的一般特性，真皮 Fb 可能提供另一种可行的细胞治疗来源。
Bone marrow mesenchymal stem cells (MSC) have potent immunosuppressive properties and have been advocated for therapeutic use in humans. The nature of their suppressive capacity is poorly understood but is said to be a primitive stem cell function. Demonstration that adult stromal cells such as fibroblasts (Fb) can modulate T cells would have important implications for immunoregulation and cellular therapy. In this report, we show that dermal Fb inhibit allogeneic T cell activation by autologously derived cutaneous APCs and other stimulators. Fb mediate suppression through soluble factors, but this is critically dependent on IFN-gamma from activated T cells. IFN-gamma induces IDO in Fb, and accelerated tryptophan metabolism is at least partly responsible for suppression of T cell proliferation. T cell suppression is reversible, and transient exposure to Fb during activation reprograms T cells, increasing IL-4 and IL-10 secretion upon restimulation. Increased Th2 polarization by stromal cells is associated with amelioration of pathological changes in a human model of graft-vs-host disease. Dermal Fb are highly clonogenic in vitro, suggesting that Fb-mediated immunosuppression is not due to outgrowth of rare MSC, although dermal Fb remain difficult to distinguish from MSC by phenotype or transdifferentiation capacity. These results suggest that immunosuppression is a general property of stromal cells and that dermal Fb may provide an alternative and accessible source of cellular therapy.