Cargando…

Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

BACKGROUND: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on difference...

Descripción completa

Detalles Bibliográficos
Autores principales: Dobbs, Katherine R., Embury, Paula, Koech, Emmily, Ogolla, Sidney, Munga, Stephen, Kazura, James W., Dent, Arlene E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938546/
https://www.ncbi.nlm.nih.gov/pubmed/33685492
http://dx.doi.org/10.1186/s12979-021-00223-2
_version_ 1783661613478313984
author Dobbs, Katherine R.
Embury, Paula
Koech, Emmily
Ogolla, Sidney
Munga, Stephen
Kazura, James W.
Dent, Arlene E.
author_facet Dobbs, Katherine R.
Embury, Paula
Koech, Emmily
Ogolla, Sidney
Munga, Stephen
Kazura, James W.
Dent, Arlene E.
author_sort Dobbs, Katherine R.
collection PubMed
description BACKGROUND: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. RESULTS: We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. CONCLUSIONS: These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-021-00223-2.
format Online
Article
Text
id pubmed-7938546
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-79385462021-03-09 Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children Dobbs, Katherine R. Embury, Paula Koech, Emmily Ogolla, Sidney Munga, Stephen Kazura, James W. Dent, Arlene E. Immun Ageing Research BACKGROUND: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. RESULTS: We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. CONCLUSIONS: These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-021-00223-2. BioMed Central 2021-03-08 /pmc/articles/PMC7938546/ /pubmed/33685492 http://dx.doi.org/10.1186/s12979-021-00223-2 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Dobbs, Katherine R.
Embury, Paula
Koech, Emmily
Ogolla, Sidney
Munga, Stephen
Kazura, James W.
Dent, Arlene E.
Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children
title Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children
title_full Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children
title_fullStr Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children
title_full_unstemmed Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children
title_short Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children
title_sort age-related differences in monocyte dna methylation and immune function in healthy kenyan adults and children
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938546/
https://www.ncbi.nlm.nih.gov/pubmed/33685492
http://dx.doi.org/10.1186/s12979-021-00223-2
work_keys_str_mv AT dobbskatheriner agerelateddifferencesinmonocytednamethylationandimmunefunctioninhealthykenyanadultsandchildren
AT emburypaula agerelateddifferencesinmonocytednamethylationandimmunefunctioninhealthykenyanadultsandchildren
AT koechemmily agerelateddifferencesinmonocytednamethylationandimmunefunctioninhealthykenyanadultsandchildren
AT ogollasidney agerelateddifferencesinmonocytednamethylationandimmunefunctioninhealthykenyanadultsandchildren
AT mungastephen agerelateddifferencesinmonocytednamethylationandimmunefunctioninhealthykenyanadultsandchildren
AT kazurajamesw agerelateddifferencesinmonocytednamethylationandimmunefunctioninhealthykenyanadultsandchildren
AT dentarlenee agerelateddifferencesinmonocytednamethylationandimmunefunctioninhealthykenyanadultsandchildren