gene expression profile analysis of in tumor-infiltrating dendritic cells (TIDC) from stress mice compared with Ctrl mice

Social defat did modify the “quality” of TIDC as manifested by massive changes in thegene expression profile. RNAseq analyses revealed signs of SD-induced localimmune suppression, as indicated by the downregulation of myeloid leukocyte differentiation, antigen signaling pathway, neutrophil chemotaxis, cell adhesion, inflammatory response stress and IFN-gamma production. Gene ontology (GO) analysis also suggested that SD amplified the circadian rhythm and cellular metabolism networks in tumor-infiltrating DC. More importantly, SD significantly augmented the level of mRNA encoding glucocorticoid-inducible transcriptional regulator Tsc22 domain family protein 3 (Tsc22d3, also known as glucocorticoid-induced leucine zipper, Gilz) , which functions as a potent mediator of anti-inflammation and immunosuppression. In addition, SD modulated the transcription of a large set of Tsc22d3 downstream target genes identified by Ingenuity® Pathway Analysis.

社交挫败可改变肿瘤浸润树突状细胞（tumor-infiltrating dendritic cells, TIDC）的功能特性，该改变可通过基因表达谱的显著重塑得以体现。RNA测序（RNAseq）分析显示，社交挫败诱导了局部免疫抑制表型，具体表现为髓系白细胞分化、抗原信号通路、中性粒细胞趋化、细胞黏附、炎症应答应激以及干扰素-γ（IFN-γ）产生相关基因的下调。基因本体（Gene Ontology, GO）分析进一步表明，社交挫败强化了肿瘤浸润树突状细胞内的昼夜节律与细胞代谢网络。更为关键的是，社交挫败显著上调了编码糖皮质激素诱导型转录调节因子Tsc22结构域家族蛋白3的mRNA水平，该因子（又称糖皮质激素诱导亮氨酸拉链蛋白Gilz，即Tsc22d3）是强效的抗炎与免疫抑制介质。此外，经Ingenuity®通路分析（Ingenuity® Pathway Analysis）鉴定得到的大量Tsc22d3下游靶基因的转录过程，也受到社交挫败的调控。