Interferon-γ and Tumor Necrosis Factor-α Polarize Bone Marrow Stromal Cells Uniformly to a Th1 Phenotype.
Interferon-γ and Tumor Necrosis Factor-α Polarize Bone Marrow Stromal Cells Uniformly to a Th1 Phenotype.
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DOI：
10.1038/srep26345
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发表时间：
2016-05-23
影响因子：
4.6
通讯作者：
Stroncek D
中科院分区：
文献类型：
--
作者：
Jin P;Zhao Y;Liu H;Chen J;Ren J;Jin J;Bedognetti D;Liu S;Wang E;Marincola F;Stroncek D
活化的T细胞将间充质基质细胞（MSC）转化为促炎性Th 1表型，这可能在放大肿瘤微环境中的免疫反应中起重要作用。我们研究了活化T细胞产生的干扰素γ（IFN-γ）和肿瘤坏死因子α（TNF-α）在MSC极化中的作用。基因表达和培养上清分析显示TNF-α和IFN-γ刺激的MSCs表达不同的促炎因子。IFN-γ和TNF-α的组合具有协同作用，并诱导了与用活化T细胞刺激的MSC中发现的转录组最相似的转录组，并且与炎症肿瘤微环境中发现的转录组相似; Th 1表型，表达免疫抑制因子IL-4、IL-10、CD 274/PD-L1和吲哚胺2，3双加氧酶（IDO）。单细胞qRT-PCR分析显示IFN-γ和TNF-α的组合均匀地极化为该表型。IFN-γ和TNF-α的组合导致MSC向主要Th 1表型的非均匀极化。从活化的肿瘤浸润性T细胞释放的IFN-γ和TNF-α对MSC的刺激可能负责产生表征肿瘤微环境的许多因子。
Activated T cells polarize mesenchymal stromal cells (MSCs) to a proinflammatory Th1 phenotype which likely has an important role in amplifying the immune response in the tumor microenvironment. We investigated the role of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), two factors produced by activated T cells, in MSC polarization. Gene expression and culture supernatant analysis showed that TNF-α and IFN-γ stimulated MSCs expressed distinct sets of proinflammatory factors. The combination of IFN-γ and TNF-α was synergistic and induced a transcriptome most similar to that found in MSCs stimulated with activated T cells and similar to that found in the inflamed tumor microenvironment; a Th1 phenotype with the expression of the immunosuppressive factors IL-4, IL-10, CD274/PD-L1 and indoleamine 2,3 dioxygenase (IDO). Single cell qRT-PCR analysis showed that the combination of IFN-γ and TNF-α polarized uniformly to this phenotype. The combination of IFN-γ and TNF-α results in the synergist uniform polarization of MSCs toward a primarily Th1 phenotype. The stimulation of MSCs by IFN-γ and TNF-α released from activated tumor infiltrating T cells is likely responsible for the production of many factors that characterize the tumor microenvironment.