Nicotine Changes the microRNA Profile to Regulate the FOXO Memory Program of CD8+ T Cells in Rheumatoid Arthritis.
Front Immunol
; 11: 1474, 2020.
Article
em En
| MEDLINE
| ID: mdl-32765511
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
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Linfócitos T CD8-Positivos
/
MicroRNAs
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Receptor de Morte Celular Programada 1
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Proteína Forkhead Box O1
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Nicotina
Tipo de estudo:
Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2020
Tipo de documento:
Article