Sex-based comparison of CD4+ T cell DNA methylation in lupus reveals proinflammatory epigenetic changes in men.
Epigenetics
Lupus
Methylation
Sex bias
T cells
Journal
Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
28
06
2022
revised:
29
08
2022
accepted:
01
09
2022
pubmed:
9
9
2022
medline:
21
9
2022
entrez:
8
9
2022
Statut:
ppublish
Résumé
Systemic lupus erythematosus (SLE) is more common in women than men, but the disease is more severe when it affects men. Lupus CD4+ T cells demonstrate dysregulated DNA methylation patterns. The purpose of this study was to investigate genome-wide CD4+ T cell differential DNA methylation between men (n = 12) and women (n = 10) with SLE. DNA methylation was evaluated using the Infinium MethylationEPIC array, and differences between male versus female SLE patients were calculated with probe-wise linear regressions with adjustment for age and disease activity. We identified 198 hypomethylated and 108 hypermethylated CpG sites in CD4+ T cells isolated from male compared to female SLE patients, annotated to 201 and 102 genes, respectively. A great proportion of these genes were related to apoptosis and immune functions. Among differentially methylated genes, CASP10, which is involved in the extrinsic apoptotic pathway, and multiple genes involved in T cell function and differentiation such as ELAVL1, UHRF1, and SMAD2, were hypomethylated in men compared to women with SLE. Importantly, network analysis of differentially methylated genes revealed a pattern consistent with increased activation of ROCK, PP2A, PI3K, and ERK1/ERK2 in men compared to women with SLE. These data provide epigenetic evidence suggesting activation of key T cell pathways in men compared to women with SLE and shed new light into possible mechanisms underlying increased SLE disease severity in men.
Identifiants
pubmed: 36075396
pii: S1521-6616(22)00197-8
doi: 10.1016/j.clim.2022.109116
pmc: PMC10236946
mid: NIHMS1903929
pii:
doi:
Substances chimiques
CCAAT-Enhancer-Binding Proteins
0
UHRF1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
109116Subventions
Organisme : NIAID NIH HHS
ID : R01 AI097134
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have declared that no conflict of interest exists.
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