{"doi":"10.3390/cells11182810","title":"Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity","abstract":"CD4+ 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.","journal":"Cells","year":2022,"id":261291,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":239127,"name":"Fatma Saaoud","orcid":null,"position":1,"is_corresponding":false},{"id":387922,"name":"William D. Cornwell","orcid":"0000-0003-3257-8424","position":2,"is_corresponding":false},{"id":237316,"name":"Keman Xu","orcid":"0000-0002-0816-1760","position":3,"is_corresponding":false},{"id":912863,"name":"Aaron M. Kirchhoff","orcid":null,"position":4,"is_corresponding":false},{"id":237313,"name":"Yifan Lu","orcid":"0000-0003-4461-0698","position":5,"is_corresponding":false},{"id":267258,"name":"Xiaohua Jiang","orcid":"0000-0003-3325-6531","position":6,"is_corresponding":false},{"id":233134,"name":"Hong Wang","orcid":"0000-0001-6258-4070","position":7,"is_corresponding":false},{"id":376536,"name":"Thomas J. Rogers","orcid":"0000-0002-9189-8105","position":8,"is_corresponding":false},{"id":233133,"name":"Xiaofeng Yang","orcid":"0000-0002-6854-6195","position":9,"is_corresponding":false},{"id":237315,"name":"Ying Shao","orcid":"0000-0001-5879-0154","position":0,"is_corresponding":true}],"reference_count":147,"raw_metadata":null,"created_at":"2026-07-19T00:26:12.158801Z","pmid":"36139385","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}