Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes
Open accessAbstract
To clarify the biological rationale for social regulation of gene expression, this study sought to identify the specific immune cell types that are transcriptionally sensitive to subjective social isolation (loneliness). Using reference distributions for the expression of each human gene in each major leukocyte subtype, we mapped the cellular origin of transcripts found to be differentially expressed in the circulating immune cells from chronically lonely individuals. Loneliness-associated genes derived primarily from plasmacytoid dendritic cells, monocytes, and, to a lesser extent, B lymphocytes. Those dynamics reflected per-cell changes in the expression of inducible genes and related more strongly to the subjective experience of loneliness than to objective social network size. Evolutionarily ancient myeloid antigen-presenting cells appear to have evolved a transcriptional sensitivity to socioenvironmental conditions that may allow them to shift basal gene expression profiles to counter the changing microbial threats associated with hostile vs. affine social conditions.
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Social isolation is related to the up-regulated expression of proinflammatory immune response genes and a reciprocal down-regulation of genes involved in antibody production.
“Social isolation has also been related to the up-regulated expression of proinflammatory immune response genes and a reciprocal down-regulation of genes involved in antibody production”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as S. W. Cole, Hawkley, Arevalo, & Cacioppo, 2011
In socially isolated individuals, up-regulated genes included inflammation-related transcripts, while down-regulated transcripts were involved in Type I interferon innate antiviral responses and antibody production.
“Genes up-regulated in socially isolated individuals included a set of transcripts that play a central role in inflammation (e.g., IL1B, IL8, PTGS2), whereas down-regulated transcripts were involved in Type I interferon innate antiviral responses (e.g., ISG, IFI, MX, and OAS family genes) and in antibody production (e.g., IGL, IGH, IGJ, and IGK) [5], [14], [15].”
From Human Social Genomics (2014) · cites this paper as [15]
Genome-wide transcriptional profiling of leukocytes from chronically socially isolated people identified more than 200 genes with more than 50% difference in average expression relative to socially integrated people.
“Genome-wide transcriptional profiling of leukocytes from people experiencing chronic social isolation identified >200 genes that showed >50% difference in average expression levels relative to those observed in socially integrated people [14], [15].”
From Human Social Genomics (2014) · cites this paper as [15]
Bioinformatic decomposition of transcriptome shifts in heterogeneous leukocytes initially identified myeloid lineage immune cells such as monocytes and dendritic cells as the primary cellular mediators of CTRA transcriptome shifts.
“Bioinformatic decomposition of transcriptome shifts in the heterogenous leukocyte population initially identified the primary cellular mediators of CTRA transcriptome shifts as myeloid lineage immune cells such as monocytes and dendritic cells [15].”
From Human Social Genomics (2014) · cites this paper as [15]
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- Authors
- Cole, S. W., Hawkley, L. C., Arevalo, J. M. G., & Cacioppo, J. T.
- Affiliations
- Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles School of Medicine, Los Angeles, CA 90095-1678;
- University of Chicago (US)
- University of California, Los Angeles (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-02-07
- Volume
- 108
- Issue
- 7
- Pages
- 3080-3085
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3041107
- OpenAlex
- W2115394480
- Cited by
- 306
- References
- 60
- Citations by year
- 2026: 10 · 2025: 28 · 2024: 11 · 2023: 18 · 2022: 16 · 2021: 26 · 2020: 17 · 2019: 28 · 2018: 19 · 2017: 16 · 2016: 27 · 2015: 21 · 2014: 22 · 2013: 24 · 2012: 17
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P01AG018911, P01 AG19811, R37AG033590, R01AG034052, P30AG028748, R01AG033590)
- National Cancer Institute (R01CA116778)
- National Institute of Allergy and Infectious Diseases (R01 AI52737, R01AI052737)
- National Center for Research Resources (P20RR020645)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Health › Health disparities and outcomes
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- social isolation, loneliness, gene expression, antigen-presenting cells, plasmacytoid dendritic cells, monocytes, B cells, leukocytes, transcriptional regulation, myeloid cells, social network size, microbial threats
- MeSH terms
- Antigen-Presenting Cells, Gene Expression Regulation, Humans, Leukocytes, Loneliness, Social Environment, Computational Biology, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Databases, Genetic
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