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Nicotine changes the microRNA profile to regulate the FOXO memory program of CD8$^{+}$ T cells in rheumatoid arthritis


Wasén, Caroline; Ospelt, Caroline; Camponeschi, Alessandro; Erlandsson, Malin C; Andersson, Karin M E; Silfverswärd, Sofia Töyrä; Gay, Steffen; Bokarewa, Maria I (2020). Nicotine changes the microRNA profile to regulate the FOXO memory program of CD8$^{+}$ T cells in rheumatoid arthritis. Frontiers in Immunology, 11:1474.

Abstract

Objective: Smoking suppresses PD-1 expression in patients with rheumatoid arthritis (RA). In this study, we assess if smoking changed the epigenetic control over CD8$^{+}$ T cell memory formation through a microRNA (miR) dependent mechanism. Methods: Phenotypes of CD8$^{+}$ T cells from smokers and non-smokers, RA and healthy, were analyzed by flow cytometry. A microarray analysis was used to screen for differences in miR expression. Sorted CD8$^{+}$ cells were in vitro stimulated with nicotine and analyzed for transcription of miRs and genes related to memory programming by qPCR. Results: CD27$^{+}$CD107a$^{-}$CD8$^{+}$ T cells, defining a naïve-memory population, had low expression of PD-1. Additionally, the CD27$^{+}$ population was more frequent in smokers (p = 0.0089). Smokers were recognized by differential expression of eight miRs. Let-7c-5p, let-7d-5p and let-7e-5p, miR-92a-3p, miR-150-5p, and miR-181-5p were up regulated, while miR-3196 and miR-4723-5p were down regulated. These miRs were predicted to target proteins within the FOXO-signaling pathway involved in CD8$^{+}$ memory programming. Furthermore, miR-92a-3p was differentially expressed in CD8$^{+}$ cells with naïve-memory predominance. Nicotine exposure of CD8$^{+}$ cells induced the expression of miR-150-5p and miR-181a-5p in the naïve-memory cells in vitro. Additionally, nicotine exposure inverted the ratio between mRNAs of proteins in the FOXO pathway and their targeting miRs. Conclusions: Smokers have a high prevalence of CD8$^{+}$ T cells with a naïve-memory phenotype. These cells express a miR profile that interacts with the memory programming conducted through the FOXO pathway.

Abstract

Objective: Smoking suppresses PD-1 expression in patients with rheumatoid arthritis (RA). In this study, we assess if smoking changed the epigenetic control over CD8$^{+}$ T cell memory formation through a microRNA (miR) dependent mechanism. Methods: Phenotypes of CD8$^{+}$ T cells from smokers and non-smokers, RA and healthy, were analyzed by flow cytometry. A microarray analysis was used to screen for differences in miR expression. Sorted CD8$^{+}$ cells were in vitro stimulated with nicotine and analyzed for transcription of miRs and genes related to memory programming by qPCR. Results: CD27$^{+}$CD107a$^{-}$CD8$^{+}$ T cells, defining a naïve-memory population, had low expression of PD-1. Additionally, the CD27$^{+}$ population was more frequent in smokers (p = 0.0089). Smokers were recognized by differential expression of eight miRs. Let-7c-5p, let-7d-5p and let-7e-5p, miR-92a-3p, miR-150-5p, and miR-181-5p were up regulated, while miR-3196 and miR-4723-5p were down regulated. These miRs were predicted to target proteins within the FOXO-signaling pathway involved in CD8$^{+}$ memory programming. Furthermore, miR-92a-3p was differentially expressed in CD8$^{+}$ cells with naïve-memory predominance. Nicotine exposure of CD8$^{+}$ cells induced the expression of miR-150-5p and miR-181a-5p in the naïve-memory cells in vitro. Additionally, nicotine exposure inverted the ratio between mRNAs of proteins in the FOXO pathway and their targeting miRs. Conclusions: Smokers have a high prevalence of CD8$^{+}$ T cells with a naïve-memory phenotype. These cells express a miR profile that interacts with the memory programming conducted through the FOXO pathway.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:2020
Deposited On:11 Aug 2020 16:26
Last Modified:12 Aug 2020 20:00
Publisher:Frontiers Research Foundation
ISSN:1664-3224
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.3389/fimmu.2020.01474
PubMed ID:32765511

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