Cigarette Smoke Modulates Inflammation and Immunity <i>via</i> Reactive Oxygen Species-Regulated Trained Immunity and Trained Tolerance Mechanisms

Saaoud, Fatma; Shao, Ying; Cornwell, William D.; Wang, Hong; Rogers, Thomas J.; Yang, Xiaofeng

doi:10.1089/ars.2022.0087

Cited by 7 publications

(5 citation statements)

References 182 publications

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“…Post-translational histone modifications are a key epigenetic mark characterizing trained immunity [ 90 ]. It has been reported that cigarette smoke affects both innate and adaptive immune responses and induces metabolic reprogramming and epigenetic chromatin modification [ 44 , 91 , 92 ]. We hypothesized that SM, M and SM + M modulate trained immunity and histone modification in Tregs.…”

Section: Resultsmentioning

confidence: 99%

“…As shown in Figure 9 , we proposed a novel working model to integrate all the findings. More than 7000 chemicals in cigarette smoke and morphine bind to the membrane and intracellular receptors for PAMPs/DAMPs and opioid receptors in the FOXP3 + Tregs and induce intracellular signaling pathways [ 44 ] and Tregs transcriptomic reshaping. Tregs can be induced by smoke plus morphine to become proinflammatory cells expressing RORC, which lose suppressive capacity while retaining FOXP3 expression.…”

Section: Discussionmentioning

confidence: 99%

“…Immune responses via innate immune macrophages [ 25 ], antigen-specific responses [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ], CD4 + Foxp3 + Treg [ 7 , 19 , 38 , 39 , 40 ], and co-signaling and immune checkpoint receptors [ 41 ] play significant roles in modulating inflammation, autoimmunity, and tumor growth. Cigarette smoke (SM) affects both innate and adaptive immunity, playing dual functions in regulating immune responses and leading to dysfunctional innate and adaptive host immunity such as T cell impairment, Treg reduction, dysregulation of the inflammatory response, and causing several inflammatory diseases including respiratory diseases, COPD, and atherosclerotic cardiovascular diseases [ 42 , 43 , 44 , 45 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

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Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity

Shao

Saaoud

Cornwell

et al. 2022

Cells

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity

Shao

Saaoud

Cornwell

et al. 2022

Cells

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“…Trained immunity serves as a new mechanism underlying chronic metabolic cardiovascular diseases. In addition, trained immunity can be a qualification criteria for environmental, metabolic, and infectious stimuli to become significant cardiovascular disease risk factors such as hyperlipidemia ( 22 – 27 ), hyperglycemia ( 28 – 30 ), hyperhomocysteinemia ( 31 , 32 ), cigarette smoke ( 12 , 33 , 34 ), hypertension, infections ( 11 , 35 ), metabolic syndrome, and obesity ( 23 , 36 , 37 ), which are different from in significant endogenous metabolites and compounds in the foods in inducing trained immunity and enhancing inflammation ( 8 , 33 ).…”

Section: Trained Immunity Is a Novel Mechanism Underlying The Pathoge...mentioning

confidence: 99%

Editorial: Insights in cardiovascular therapeutics 2022—cardiovascular innate immunity

Zhang

Saaoud

et al. 2023

Front. Cardiovasc. Med.

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“…Cigarette smoke contains over 60 known chemical carcinogens that damage DNA, leading to tumour induction and also acting in later phases of carcinogenesis [ 12 ]. In addition, exposure to cigarette smoke causes chronic inflammation and alterations in systemic immunity that may favour cancer promotion/progression [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Lung Adenocarcinoma Diagnosed at a Younger Age Is Associated with Advanced Stage, Female Sex, and Ever-Smoker Status, in Patients Treated with Lung Resection

Dragani

Muley

Schneider

et al. 2023

Cancers

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To date, the factors which affect the age at diagnosis of lung adenocarcinoma are not fully understood. In our study, we examined the relationships of age at diagnosis with smoking, pathological stage, sex, and year of diagnosis in a discovery (n = 1694) and validation (n = 1384) series of lung adenocarcinoma patients who had undergone pulmonary resection at hospitals in the Milan area and at Thoraxklinik (Heidelberg), respectively. In the discovery series, younger age at diagnosis was associated with ever-smoker status (OR = 1.5, p = 0.0035) and advanced stage (taking stage I as reference: stage III OR = 1.4, p = 0.0067; stage IV OR = 1.7, p = 0.0080), whereas older age at diagnosis was associated with male sex (OR = 0.57, p < 0.001). Analysis in the validation series confirmed the ever versus never smokers’ association (OR = 2.9, p < 0.001), the association with highest stages (stage III versus stage I OR = 1.4, p = 0.0066; stage IV versus stage I OR = 2.0, p = 0.0022), and the male versus female sex association (OR = 0.78, p = 0.032). These data suggest the role of smoking in affecting the natural history of the disease. Moreover, aggressive tumours seem to have shorter latency from initiation to clinical detection. Finally, younger age at diagnosis is associated with the female sex, suggesting that hormonal status of young women confers risk to develop lung adenocarcinoma. Overall, this study provided novel findings on the mechanisms underlying age at diagnosis of lung adenocarcinoma.

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Cigarette Smoke Modulates Inflammation and Immunity via Reactive Oxygen Species-Regulated Trained Immunity and Trained Tolerance Mechanisms

Cited by 7 publications

References 182 publications

Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity

Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity

Editorial: Insights in cardiovascular therapeutics 2022—cardiovascular innate immunity

Lung Adenocarcinoma Diagnosed at a Younger Age Is Associated with Advanced Stage, Female Sex, and Ever-Smoker Status, in Patients Treated with Lung Resection

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