Introduction: 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.
Material and methods: 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.
Results: 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.
Conclusions: Smoking specifically alters vital immune regulation genes in lymphocyte subtypes, especially CD4+, CD8+ and CD14+ cells.
Keywords: B cell; C-type lectin domain family; T cell; expression profiling; lymphocyte; macrophage; monocyte; smoking; ulcerative colitis.
Copyright © 2022 Termedia.