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Age-associated DNA methylation changes in naive CD4+ T cells suggest an evolving autoimmune epigenotype in aging T cells.
Dozmorov, Mikhail G; Coit, Patrick; Maksimowicz-McKinnon, Kathleen; Sawalha, Amr H.
Afiliación
  • Dozmorov MG; Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Coit P; Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
  • Maksimowicz-McKinnon K; Division of Rheumatology, Henry Ford Health System, Detroit, MI 48202, USA.
  • Sawalha AH; Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Epigenomics ; 9(4): 429-445, 2017 04.
Article en En | MEDLINE | ID: mdl-28322571
AIM: We sought to define age-associated DNA methylation changes in naive CD4+ T cells. MATERIALS & METHODS: Naive CD4+ T cells were collected from 74 healthy individuals (age 19-66 years), and age-related DNA methylation changes were characterized. RESULTS: We identified 11,431 age-associated CpG sites, 57% of which were hypermethylated with age. Hypermethylated sites were enriched in CpG islands and repressive transcription factor binding sites, while hypomethylated sites showed T cell specific enrichment in active enhancers marked by H3K27ac and H3K4me1. Our data emphasize cancer-related DNA methylation changes with age, and also reveal age-associated hypomethylation in immune-related pathways, such as T cell receptor signaling, FCγR-mediated phagocytosis, apoptosis and the mammalian target of rapamycin signaling pathway. The MAPK signaling pathway was hypermethylated with age, consistent with a defective MAPK signaling in aging T cells. CONCLUSION: Age-associated DNA methylation changes may alter regulatory mechanisms and signaling pathways that predispose to autoimmunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Linfocitos T CD4-Positivos / Autoinmunidad / Epítopos de Linfocito T / Metilación de ADN / Epigenómica Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Epigenomics Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Linfocitos T CD4-Positivos / Autoinmunidad / Epítopos de Linfocito T / Metilación de ADN / Epigenómica Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Epigenomics Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido