表鞘苷-1-磷酸将健康单核细胞塑造成免疫抑制表型

IF 2.5 Q3 CELL BIOLOGY Cellular Physiology and Biochemistry Pub Date : 2024-03-17 DOI:10.33594/000000691
Michela Terlizzi, Anna Falanga, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino
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引用次数: 0

摘要

背景/目的:个体的生理表型可影响和塑造现实生活中的现象,因为它有助于形成特定的特征,从而影响对特定刺激的免疫反应。本研究旨在了解鞘磷脂/鞘氨醇-1-磷酸(S1P)轴是否能调节循环细胞的免疫表型:为了实现这一目标,我们对公开数据集进行了生物信息学分析:结果:GSE192829 数据集中健康受试者的转录组图谱发现了两个具有不同转录谱的集群。群组 1 表达了较高水平的 S1P 形成酶,而群组 0 的特点是表达了导致神经酰胺形成的酶,这代表了相反的代谢方向。推理分析表明,群组 1 中的单核细胞、CD4+ T 细胞和 B 细胞的数量高于群组 0。其他数据集分析证实了 S1P 特征在健康 PBMCs 中的作用,证明神经酰胺酶阳性的循环单核细胞与阴性单核细胞不同,具有以枢纽免疫抑制标记(即 TYROBP、FCER1G、SYK、SIRPA、CSF1R、AIF1、FCGR2A、CLEC7A、LYN、PLCG2、LILRs、HCK、GAB2)为特征的免疫抑制表型。该中心基因很好地区分了健康受试者的免疫类型:总之,本研究强调了 S1P 相关枢纽标记物可用于区分免疫抑制明显的受试者。
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Sphingosine-1-Phosphate Shapes Healthy Monocytes into An Immunosuppressive Phenotype.

Background/aims: The physiological phenotype of individuals can influence and shape real-life phenomena in that it can contribute to the development of specific characteristics that can affect the immune response to specific stimuli. In this study we aimed to understand whether the sphingosine/sphingosine-1-phoshate (S1P) axis can modulate the immunotype of circulating cells.

Methods: To pursue this goal, we performed bioinformatic analyses of public datasets.

Results: The transcriptomic profile of healthy subjects of GSE192829 dataset identified two clusters with different transcriptional repertoire. Cluster 1 expressed higher levels of enzymes for S1P formation than cluster 0 which was characterized by enzymes that lead to ceramide formation, which represent the opposite metabolic direction. Inference analysis showed that cluster 1 was higher populated by monocytes, CD4+ T and B cells than cluster 0. Of particular interest was the phenotype of the monocytes in cluster 1 which showed an immunosuppressive nature compared to those in cluster 0. The role of S1P signature in healthy PBMCs was confirmed with other dataset analyses, supporting that circulating monocytes positive to the ceramidase, unlike the negative ones, had an immunosuppressive phenotype characterized by hub immunosuppressive markers (i.e. TYROBP, FCER1G, SYK, SIRPA, CSF1R, AIF1, FCGR2A, CLEC7A, LYN, PLCG2, LILRs, HCK, GAB2). This hub genes well discriminated the immunotype of healthy subjects.

Conclusion: In conclusion this study highlights that S1P-associated hub markers can be useful to discriminate subjects with pronounced immunosuppression.

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来源期刊
CiteScore
5.80
自引率
0.00%
发文量
86
审稿时长
1 months
期刊介绍: Cellular Physiology and Biochemistry is a multidisciplinary scientific forum dedicated to advancing the frontiers of basic cellular research. It addresses scientists from both the physiological and biochemical disciplines as well as related fields such as genetics, molecular biology, pathophysiology, pathobiochemistry and cellular toxicology & pharmacology. Original papers and reviews on the mechanisms of intracellular transmission, cellular metabolism, cell growth, differentiation and death, ion channels and carriers, and the maintenance, regulation and disturbances of cell volume are presented. Appearing monthly under peer review, Cellular Physiology and Biochemistry takes an active role in the concerted international effort to unravel the mechanisms of cellular function.
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