Specific induction of the unique GPR15 expression in heterogeneous blood lymphocytes by tobacco smoking

Bauer, Mario; Hackermüller, Jörg; Schor, Jana; Schreiber, S; Fink, Beate; Pierzchalski, Arkadiusz; Herberth, Gunda

doi:10.1080/1354750x.2018.1539769

Cited by 16 publications

(19 citation statements)

References 32 publications

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“…Although they have been associated with a variety of inflammatory conditions, the biological role of GPR15+ expressing T cells is not clear. Bauer [45] and colleagues recently demonstrated that GPR15 expression was not specific to any T cell subtype, although it was most expressed on T h 17 cells, and suggested a potentially protective role for GPR15-expressing T cells in chronic smoking. Going forward, further mechanistic studies are needed to establish whether GPR15-expressing T cells convey risk, benefit, or neither in smokers and whether they may be targets for therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

“…Kim [48] found that mice deficient in GPR15 developed severe large intestinal inflammation, suggesting a potentially protective role in immune homeostasis, while Bauer and colleagues [49] found that the level of GPR15-expressing T cells was unrelated to the lung disease status in human smokers and non-smokers. Bauer and colleagues [45] also found that smoking was associated with increased GPR15 expression across a broad range of T cell subtypes in adults, suggesting GPR15+ T cells may be adaptive rather than pathogenic.…”

Section: Introductionmentioning

confidence: 95%

“…Lastly, in contrast to cg19859270, smoking-associated hypomethylation of cg05575921 is not influenced by genetic background, providing additional utility as a tool for investigating smoking's biological effects in populations of mixed ancestry [28]. Lastly, in contrast to cg19859270, hypomethylation of cg05575921 has been shown in multiple studies to primarily occur in granulocytes and monocytes, suggesting a distinct role for these cell populations in biological responses to smoking [45,46].…”

Section: Introductionmentioning

confidence: 96%

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Cigarette and Cannabis Smoking Effects on GPR15+ Helper T Cell Levels in Peripheral Blood: Relationships with Epigenetic Biomarkers

Andersen

Lei

Beach

et al. 2020

Genes

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Background: Smoking causes widespread epigenetic changes that have been linked with an increased risk of smoking-associated diseases and elevated mortality. Of particular interest are changes in the level of T cells expressing G-protein-coupled receptor 15 (GPR15), a chemokine receptor linked with multiple autoimmune diseases, including inflammatory bowel disease, multiple sclerosis and psoriasis. Accordingly, a better understanding of the mechanisms by which smoking influences variation in the GPR15+ helper T cell subpopulation is of potential interest. Methods: In the current study, we used flow cytometry and digital PCR assays to measure the GPR15+CD3+CD4+ populations in peripheral blood from a cohort of n = 62 primarily African American young adults (aged 27–35 years) with a high rate of tobacco and cannabis use. Results: We demonstrated that self-reported tobacco and cannabis smoking predict GPR15+CD3+CD4+ helper T cell levels using linear regression models. Further, we demonstrated that methylation of two candidate CpGs, cg19859270, located in GPR15, and cg05575921, located in the gene Aryl Hydrocarbon Receptor Repressor (AHRR), were both significant predictors of GPR15+CD3+CD4+ cell levels, mediating the relationship between smoking habits and increases in GPR15+CD3+CD4+ cells. As hypothesized, the interaction between cg05575921 and cg19859270 was also significant, indicating that low cg05575921 methylation was more strongly predictive of GPR15+CD3+CD4+ cell levels for those who also had lower cg19859270 methylation. Conclusions: Smoking leads changes in two CpGs, cg05575921 and cg19859270, that mediate 38.5% of the relationship between tobacco and cannabis smoking and increased GPR15+ Th levels in this sample. The impact of cg19859270 in amplifying the association between cg05575921 and increased GPR15+ Th levels is of potential theoretical interest given the possibility that it reflects a permissive interaction between different parts of the adaptive immune system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 96%

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Cigarette and Cannabis Smoking Effects on GPR15+ Helper T Cell Levels in Peripheral Blood: Relationships with Epigenetic Biomarkers

Andersen

Lei

Beach

et al. 2020

Genes

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“…, overlap). Notably, smoking is the only condition known to increase the numbers of GPR15+ T cells in blood which are pro‐inflammatory Th17‐like . GPR15 is an orphan receptor that is involved in the regulation of the innate immunity and T‐cell trafficking .…”

Section: Discussionmentioning

confidence: 99%

Smoking affects gene expression in blood of patients with ischemic stroke

Cheng

Ferino

Hull

et al. 2019

Ann Clin Transl Neurol

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Objective Though cigarette smoking (CS) is a well‐known risk factor for ischemic stroke (IS), there is no data on how CS affects the blood transcriptome in IS patients. Methods We recruited IS‐current smokers (IS‐SM), IS‐never smokers (IS‐NSM), control‐smokers (C‐SM), and control‐never smokers (C‐NSM). mRNA expression was assessed on HTA‐2.0 microarrays and unique as well as commonly expressed genes identified for IS‐SM versus IS‐NSM and C‐SM versus C‐NSM. Results One hundred and fifty‐eight genes were differentially expressed in IS‐SM versus IS‐NSM; 100 genes were differentially expressed in C‐SM versus C‐NSM; and 10 genes were common to both IS‐SM and C‐SM (P < 0.01; |fold change| ≥ 1.2). Functional pathway analysis showed the 158 IS‐SM‐regulated genes were associated with T‐cell receptor, cytokine–cytokine receptor, chemokine, adipocytokine, tight junction, Jak‐STAT, ubiquitin‐mediated proteolysis, and adherens junction signaling. IS‐SM showed more altered genes and functional networks than C‐SM. Interpretation We propose some of the 10 genes that are elevated in both IS‐SM and C‐SM (GRP15, LRRN3, CLDND1, ICOS, GCNT4, VPS13A, DAP3, SNORA54, HIST1H1D, and SCARNA6) might contribute to increased risk of stroke in current smokers, and some genes expressed by blood leukocytes and platelets after stroke in smokers might contribute to worse stroke outcomes that occur in smokers.

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“…In TESA cluster 1, genes related to neutrophils, such as OLFM4, DEFA3, and DEFA4, were upregulated. The expression of GPR15, which was associated with smoking and T-cell homing, 6,7 was increased in TESA cluster 3. In TESA cluster 4, OLFM4, DEFA4, MMP8, and ELANE expressions were increased.…”

Section: To the Editormentioning

confidence: 99%

Identification of whole blood gene expressions correlated with responsiveness to benralizumab

Nakajima

Matsuyama

Arai

et al. 2021

Journal of Allergy and Clinical Immunology

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Specific induction of the unique GPR15 expression in heterogeneous blood lymphocytes by tobacco smoking

Cited by 16 publications

References 32 publications

Cigarette and Cannabis Smoking Effects on GPR15+ Helper T Cell Levels in Peripheral Blood: Relationships with Epigenetic Biomarkers

Cigarette and Cannabis Smoking Effects on GPR15+ Helper T Cell Levels in Peripheral Blood: Relationships with Epigenetic Biomarkers

Smoking affects gene expression in blood of patients with ischemic stroke

Identification of whole blood gene expressions correlated with responsiveness to benralizumab

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