ELTE NAP Neuroimmunology Research Group, Department of Biochemistry, Institute of Biology, ELTE Eötvös Loránd University, Budapest, Hungary.
Laboratory of Proteomics, Institute of Biology, ELTE Eötvös Loránd University, Budapest, Hungary.
Front Immunol. 2021 Oct 25;12:749433. doi: 10.3389/fimmu.2021.749433. eCollection 2021.
The investigation of the molecular background of direct communication of neurons and immune cells in the brain is an important issue for understanding physiological and pathological processes in the nervous system. Direct contacts between brain-infiltrating immune cells and neurons, and the neuromodulatory effect of immune cell-derived regulatory peptides are well established. Several aspects of the role of immune and glial cells in the direct neuro-immune communication are also well known; however, there remain many questions regarding the molecular details of signaling from neurons to immune cells. Thus, we report here on the neuronal expression of genes encoding antimicrobial and immunomodulatory peptides, as well as proteins of immune cell-specific activation and communication mechanisms. In the present study, we analyzed the single-cell sequencing data of our previous transcriptomic work, obtained from electrophysiologically identified pyramidal cells and interneurons of the murine prefrontal cortex. We filtered out the genes that may be associated with the direct communication between immune cells and neurons and examined their expression pattern in the neuronal transcriptome. The expression of some of these genes by cortical neurons has not yet been reported. The vast majority of antimicrobial (53%) and immune cell protein (94%) transcripts was identified in the transcriptome of the 84 cells, owing to the high sensitivity of ultra-deep sequencing. Several of the antimicrobial and immune process-related protein transcripts showed cell type-specific or enriched expression. Individual neurons transcribed only a fraction of the investigated genes with low copy numbers probably due to the bursting kinetics of gene expression; however, the comparison of our data with available transcriptomic datasets from immune cells and neurons suggests the functional relevance of the reported findings. Accordingly, we propose further experimental and studies on the neuronal expression of immune system-related genes and the potential role of the encoded proteins in neuroimmunological processes.
研究神经元和脑内免疫细胞直接通讯的分子基础,是理解神经系统生理和病理过程的重要问题。脑内浸润免疫细胞与神经元之间的直接接触,以及免疫细胞衍生的调节肽的神经调节作用,已得到充分证实。免疫细胞和神经胶质细胞在直接神经免疫通讯中的几个方面的作用也广为人知;然而,关于神经元向免疫细胞传递信号的分子细节仍存在许多问题。因此,我们在此报告神经元表达编码抗菌肽和免疫调节肽的基因,以及免疫细胞特异性激活和通讯机制的蛋白。在本研究中,我们分析了我们之前转录组学工作的单细胞测序数据,这些数据来自电生理鉴定的小鼠前额叶皮层的锥体神经元和中间神经元。我们筛选出可能与免疫细胞和神经元之间直接通讯相关的基因,并检查它们在神经元转录组中的表达模式。这些基因中的一些在皮质神经元中的表达尚未被报道。由于超高深度测序的高灵敏度,在 84 个细胞的转录组中鉴定出了绝大多数抗菌肽(53%)和免疫细胞蛋白(94%)的转录本。几种与抗菌肽和免疫过程相关的蛋白转录本表现出细胞类型特异性或富集表达。由于基因表达的爆发动力学,单个神经元仅转录了所研究基因的一小部分,拷贝数较低;然而,将我们的数据与免疫细胞和神经元的现有转录组数据集进行比较,表明了所报道发现的功能相关性。因此,我们建议进一步研究神经元表达免疫系统相关基因的情况,以及这些编码蛋白在神经免疫过程中的潜在作用。