Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity
Rogers, Thomas J.
GroupCenter for Inflammation and Lung Research (Temple University)
Center for Metabolic Disease Research (Temple University)
Cigarette smoke plus morphine
Regulatory T-cells (Treg)
Knowledge-based transcriptomic analysis
Permanent link to this recordhttp://hdl.handle.net/20.500.12613/8252
MetadataShow full item record
AbstractCD4+ regulatory T cells (Tregs) respond to environmental cues to permit or suppress inflammation, and atherosclerosis weakens Treg suppression and promotes plasticity. However, the effects of smoking plus morphine (SM + M) on Treg plasticity remain unknown. To determine whether SM + M promotes Treg plasticity to T helper 17 (Th17) cells, we analyzed the RNA sequencing data from SM, M, and SM + M treated Tregs and performed knowledge-based and IPA analysis. We demonstrated that (1) SM + M, M, and SM upregulated the transcripts of cytokines, chemokines, and clusters of differentiation (CDs) and modulated the transcripts of kinases and phosphatases in Tregs; (2) SM + M, M, and SM upregulated the transcripts of immunometabolism genes, trained immunity genes, and histone modification enzymes; (3) SM + M increased the transcripts of Th17 transcription factor (TF) RORC and Tfh factor CXCR5 in Tregs; M increased the transcripts of T helper cell 1 (Th1) TF RUNX3 and Th1-Th9 receptor CXCR3; and SM inhibited Treg TGIF1 transcript; (4) six genes upregulated in SM + M Tregs were matched with the top-ranked Th17 pathogenic genes; and 57, 39 genes upregulated in SM + M Tregs were matched with groups II and group III Th17 pathogenic genes, respectively; (5) SM + M upregulated the transcripts of 70 IPA-TFs, 11 iTregs-specific TFs, and 4 iTregs-Th17 shared TFs; and (6) SM + M, M, and SM downregulated Treg suppression TF Rel (c-Rel); and 35 SM + M downregulated genes were overlapped with Rel−/− Treg downregulated genes. These results provide novel insights on the roles of SM + M in reprogramming Treg transcriptomes and Treg plasticity to Th17 cells and novel targets for future therapeutic interventions involving immunosuppression in atherosclerotic cardiovascular diseases, autoimmune diseases, transplantation, and cancers.
CitationShao Y, Saaoud F, Cornwell W, Xu K, Kirchhoff A, Lu Y, Jiang X, Wang H, Rogers TJ, Yang X. Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity. Cells. 2022; 11(18):2810. https://doi.org/10.3390/cells11182810
Citation to related workMDPI
Has partCells, Vol. 11, No. 18
Collection "Cellular and Molecular Mechanisms of Atherosclerosis"
ADA complianceFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact email@example.com