Immune cell-specific smoking-related expression characteristics are revealed by re-analysis of transcriptomes from the CEDAR cohort

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 over -expression 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.

Automated summary

This study found that smoking specifically alters vital immune regulation genes in lymphocyte subtypes, especially CD4*, CD8*, and CD14* cells.