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Age-related Differences in Monocyte DNA Methylation and Immune Function in Healthy Kenyan Adults and Children
Arlene Elizabeth Dent
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
Corresponding Author
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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 profi 24 les 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.
Keywords
Monocyte, DNA methylation, epigenetic, ageing, aging, innate immune
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Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.
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- 20200916Table1Monocytediffchildadult.pdf
- Additionalfile1TableS1.FigureS1.pdf
- Additionalfile2DMPsKenyanchildvsKenyanadult.csv
- Additionalfile3DMRsKenyanchildvsKenyanadult.csv.csv
- Additionalfile4KEGGmethKenyanchildvsKenyanadult.csv
- Additionalfile5DESeq2KenyanchildvsKenyanadult.csv
- Additionalfile6DMPsKenyanchildvsUSadult.csv
- Additionalfile7DMPsKenyanadultvsUSadult.csv
- Additionalfile8KEGGmethKenyanadultvsUSadult.csv
- Additionalfile9DESeq2KenyanadultvsUSadult.csv
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CURRENT STATUS: Under Revision
Version 1
Posted 29 Sep, 2020
No community comments so far
Editorial decision: Major Revision
On 18 Jan, 2021
Review #2 received
Received 15 Jan, 2021
Reviewer #2 agreed
On 30 Dec, 2020
Review #1 received
Received 08 Oct, 2020
Reviewers invited
Invitations sent on 25 Sep, 2020
Reviewer #1 agreed
On 25 Sep, 2020
Editor assigned
On 21 Sep, 2020
Submission checks complete
On 20 Sep, 2020
Editor invited
On 20 Sep, 2020
First submitted
On 18 Sep, 2020
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Subject Areas
Immunology
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This preprint is under consideration at Immunity & Ageing. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Age-related Differences in Monocyte DNA Methylation and Immune Function in Healthy Kenyan Adults and Children
Arlene Elizabeth Dent
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 29 Sep, 2020
No community comments so far
Editorial decision: Major Revision
On 18 Jan, 2021
Review #2 received
Received 15 Jan, 2021
Reviewer #2 agreed
On 30 Dec, 2020
Review #1 received
Received 08 Oct, 2020
Reviewers invited
Invitations sent on 25 Sep, 2020
Reviewer #1 agreed
On 25 Sep, 2020
Editor assigned
On 21 Sep, 2020
Submission checks complete
On 20 Sep, 2020
Editor invited
On 20 Sep, 2020
First submitted
On 18 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Immunology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 profi 24 les 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.
Figure 1
Figure 2
Figure 3
Figure 4
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.
Due to technical limitations, table 1 is only available as a download in the Supplemental Files section.