Abstract in
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Myeloid-derived suppressor cells (MDSCs) are functionally immunosuppressive cells that arise and expand during extensive inflammatory conditions by increased hematopoietic output or reprogramming of immune cells. In sepsis, an increase of circulating MDSCs is associated with adverse outcomes, but unique traits that can be used to identify increased activity of MDSCs are lacking. By using endotoxin tolerance as a model of sepsis-induced monocytic MDSCs (M-MDSC-like cells), this study aims to identify the mediator and transcriptional regulator profile associated with M-MDSC activity. After analyzing 180 inflammation-associated proteins, a profile of differentially expressed cytokines was found in M-MDSC-like cells versus normal monocytes stimulated with LPS. These cytokines were associated with 5 candidate transcription factors, where particularly PU.1 showed differential expression on both transcriptional and protein levels in M-MDSC-like cells. Furthermore, inhibition of PU.1 led to increased production of CXCL5 and CCL8 in M-MDSC-like cells indicating its role in regulating the ability of M-MDSC-like cells to recruit other immune cells. Taken together, the study identifies a unique profile in the pattern of immune mediators defining M-MDSC activity upon LPS stimulation, which offers a functional link to their contribution to immunosuppression.
Differential cytokine response in endotoxin induced M-MDSC-like cells and their associated regulators.
Cytokine responses to LPS in reprogrammed monocytes are associated with the transcription factor PU.1
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组织水平：空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析：流式数据分析、组化数据分析、多因子数据分析
基因水平：PCR Array、RT-PCR、PCR、单细胞测序
蛋白水平：MSD、Luminex、CBA、Elispot、Antibody Array、ELISA、Sengenics
细胞水平：细胞染色、细胞分选、细胞培养、细胞功能
组织水平：空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析：流式数据分析、组化数据分析、多因子数据分析
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