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. 2012 Dec 11;109(50):20578-83.
doi: 10.1073/pnas.1218253109. Epub 2012 Nov 26.

Transcriptional modulation of the developing immune system by early life social adversity

Steven W Cole  1 , Gabriella Conti, Jesusa M G Arevalo, Angela M Ruggiero, James J Heckman, Stephen J Suomi
Affiliations

Transcriptional modulation of the developing immune system by early life social adversity

Steven W Cole et al. Proc Natl Acad Sci U S A. .

Abstract

To identify molecular mechanisms by which early life social conditions might influence adult risk of disease in rhesus macaques (Macaca mulatta), we analyze changes in basal leukocyte gene expression profiles in 4-mo-old animals reared under adverse social conditions. Compared with the basal condition of maternal rearing (MR), leukocytes from peer-reared (PR) animals and PR animals provided with an inanimate surrogate mother (surrogate/peer reared, SPR) show enhanced expression of genes involved in inflammation, cytokine signaling, and T-lymphocyte activation, and suppression of genes involved in several innate antimicrobial defenses including type I interferon (IFN) antiviral responses. Promoter-based bioinformatic analyses implicate increased activity of CREB and NF-κB transcription factors and decreased activity of IFN response factors (IRFs) in structuring the observed differences in gene expression. Transcript origin analyses identify monocytes and CD4(+) T lymphocytes as primary cellular mediators of transcriptional up-regulation and B lymphocytes as major sources of down-regulated genes. These findings show that adverse social conditions can become embedded within the basal transcriptome of primate immune cells within the first 4 mo of life, and they implicate sympathetic nervous system-linked transcription control pathways as candidate mediators of those effects and potential targets for health-protective intervention.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Differential gene expression in leukocytes from mother-reared vs. surrogate/peer-reared macaques. (A) Heat plot representation of gene expression values for 249 transcripts showing a twofold or greater difference in average expression between peripheral blood mononuclear cells (PBMCs) from surrogate/peer-reared (SPR) rhesus macaques and those from maternally reared (MR) rhesus macaques. Rows, animals; columns, gene transcripts; red, up-regulated gene expression; green, down-regulated gene expression. (B) Transcript origin analyses assessing cellular origins of differentially expressed genes within specific PBMC subsets. (C) Relative prevalence of binding motifs for NF-κB, IRF, CREB, and GR transcription factors within promoters of genes up-regulated in PBMCs from SPR vs. MR animals.
Fig. 2.
Fig. 2.
Differential gene expression in leukocytes from mother-reared vs. peer-reared macaques. (A) Heat plot representation of gene expression values for 256 transcripts showing a twofold or greater difference in average expression between PBMCs from peer-reared (PR) rhesus macaques and those from maternally reared (MR) rhesus macaques. (B) Transcript origin analyses assessing cellular origins of differentially expressed genes within specific PBMC subsets. (C) Relative prevalence of binding motifs for NF-κB, IRF, CREB, and GR transcription factors within promoters of genes up-regulated in PBMCs from PR vs. MR animals.
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