Nowak Jan Krzysztof, Dybska Emilia, Adams Alex T, Walkowiak Jaroslaw
Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland.
Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Cent Eur J Immunol. 2022;47(3):246-259. doi: 10.5114/ceji.2022.120618. Epub 2022 Nov 16.
Smoking is known to affect whole-blood expression and methylation profiles. Although whole-genome methylation studies indicated that effects observed in blood may be driven by changes within leukocyte subtypes, these phenomena have not been explored using expression profiling.
This study reanalyzed data from the Correlated Expression and Disease Association Research (CEDAR) patient cohort recruited by Momozawa et al. (E-MTAB-6667). Data from gene expression profiling of immunomagnetically sorted CD4, CD8, CD14, CD15, and CD19 cells were processed. Differential expression analyses were conducted in each immune cell type, followed by gene ontology analysis and supplementary investigations.
Ninety-four differentially expressed genes were found (CD8 n = 58, CD14 n = 20, CD4 n = 14, CD19 n = 2). Two key smoking-related genes were overexpressed in specific cell types: LRRN3 (CD4, CD8) and MMP25 (CD8, CD14). In CD4 cells smoking was associated with reduced expression of the NK cell receptor KLRB1, suggesting CD4 subpopulation shifts and differences in interferon signaling (reduced IRF1 and IL18RAP in smokers). Key results and their integration with an immune protein-protein interaction network revealed that smoking influences integrins in CD8 cells (ITGB7, ITGAL, ITGAM, ITGB2). C-type lectin CLEC4A was reduced in CD8 cells and CLEC10A was increased in CD14 cells from smokers; moreover, CLEC5A (CD8), CLEC7A (CD8) and CLEC9A (CD19) were related to smoking in supplementary analyses. CD14 cells from smokers exhibited overexpression of LDLR and the formyl peptide receptor FPR3.
Smoking specifically alters vital immune regulation genes in lymphocyte subtypes, especially CD4, CD8 and CD14 cells.
众所周知，吸烟会影响全血表达和甲基化谱。尽管全基因组甲基化研究表明，在血液中观察到的影响可能是由白细胞亚型内的变化驱动的，但这些现象尚未通过表达谱分析进行探索。
本研究重新分析了Momozawa等人招募的相关表达与疾病关联研究（CEDAR）患者队列的数据（E-MTAB-6667）。对免疫磁珠分选的CD4、CD8、CD14、CD15和CD19细胞的基因表达谱数据进行了处理。在每种免疫细胞类型中进行差异表达分析，随后进行基因本体分析和补充研究。
发现了94个差异表达基因（CD8中有58个，CD14中有20个，CD4中有14个，CD19中有2个）。两个与吸烟相关的关键基因在特定细胞类型中过表达：LRRN3（CD4、CD8）和MMP25（CD8、CD14）。在CD4细胞中，吸烟与自然杀伤细胞受体KLRB1的表达降低有关，提示CD4亚群发生改变以及干扰素信号传导存在差异（吸烟者中IRF1和IL18RAP降低）。关键结果及其与免疫蛋白质-蛋白质相互作用网络的整合显示，吸烟会影响CD8细胞中的整合素（ITGB7、ITGAL、ITGAM、ITGB2）。吸烟者CD8细胞中的C型凝集素CLEC4A减少，CD14细胞中的CLEC10A增加；此外，在补充分析中，CLEC5A（CD8）、CLEC7A（CD8）和CLEC9A（CD19）与吸烟有关。吸烟者的CD14细胞表现出低密度脂蛋白受体（LDLR）和甲酰肽受体FPR3的过表达。
吸烟特异性地改变淋巴细胞亚型中重要的免疫调节基因，尤其是CD4、CD8和CD14细胞。
