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首页> 外文期刊>Clinical and Experimental Immunology: An Official Journal of the British Society for Immunology >Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells.
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Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells.

机译：γ干扰素不会破坏，但会促进成人间充质干细胞的免疫抑制能力。

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The ability of mesenchymal stem cells (MSC) to suppress alloresponsiveness is poorly understood. Herein, an allogeneic mixed lymphocyte response was used as a model to investigate the mechanisms of MSC-mediated immunomodulation. Human MSC are demonstrated to express the immunosuppressive cytokines hepatocyte growth factor (HGF), interleukin (IL)-10 and transforming growth factor (TGF)-beta1 at concentrations that suppress alloresponses in vitro. MSC also express cyclooxygenase 1 and 2 and produce prostaglandin E2 constitutively. Blocking studies with indomethacin confirmed that prostaglandins contribute to MSC-mediated allosuppression. The proinflammatory cytokine interferon (IFN)-gamma did not ablate MSC inhibition of alloantigen-driven proliferation but up-regulated HGF and TGF-beta1. IFN-gamma also induced expression of indoleamine 2,3, dioxygenase (IDO), involved in tryptophan catabolism. Use of an antagonist, 1-methyl-L-tryptophan, restored alloresponsiveness and confirmed an IDO contribution to IFN-gamma-induced immunomodulation by MSC. Addition of the tryptophan catabolite kynurenine to mixed lymphocyte reactions (MLR), blocked alloproliferation. These findings support a model where IDO exerts its effect through the local accumulation of tryptophan metabolites rather than through tryptophan depletion. Taken together, these data demonstrate that soluble factors, or products derived from MSC, modulate immune responses and suggest that MSC create an immunosuppressive microenvironment capable of modulating alloresponsiveness even in the presence of IFN-gamma.
机译：间充质干细胞（MSC）抑制同种异体反应能力的了解甚少。在本文中，同种异体混合淋巴细胞反应被用作模型来研究MSC介导的免疫调节的机制。人类MSC被证明可以在体外抑制免疫反应的浓度下表达免疫抑制细胞因子肝细胞生长因子（HGF），白介素（IL）-10和转化生长因子（TGF）-beta1。 MSC还表达环氧合酶1和2，并组成性地产生前列腺素E2。用吲哚美辛进行的阻断研究证实，前列腺素有助于MSC介导的同种异体抑制。促炎性细胞因子干扰素（IFN）-γ不会消除MSC对同种抗原驱动的增殖的抑制作用，但会上调HGF和TGF-β1。 IFN-γ还诱导参与色氨酸分解代谢的吲哚胺2,3，双加氧酶（IDO）的表达。使用拮抗剂1-甲基-L-色氨酸可恢复同种异体反应性，并确认IDO对MSC的IFN-γ诱导的免疫调节有贡献。将色氨酸分解代谢物犬尿氨酸添加到混合淋巴细胞反应（MLR）中，阻止了同种异体增殖。这些发现支持了一种模型，其中IDO通过色氨酸代谢产物的局部积累而不是通过色氨酸耗竭发挥作用。综上所述，这些数据表明可溶性因子或衍生自MSC的产物可调节免疫应答，并暗示MSC可形成一种免疫抑制微环境，即使在存在IFN-γ的情况下也能调节同种异体反应性。

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