title: Transcriptional modulation of the developing immune system by early life social adversity.
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.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of California School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
authors.forename: Gabriella
authors.initials: G
authors.lastname: Conti
authors.forename: Jesusa M G
authors.initials: JM
authors.lastname: Arevalo
authors.forename: Angela M
authors.initials: AM
authors.lastname: Ruggiero
authors.forename: James J
authors.initials: JJ
authors.lastname: Heckman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Suomi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019295:Computational Biology; D030541:Databases, Genetic; D005260:Female; D008253:Macaca mulatta / Q000235:genetics* / Q000276:immunology* / Q000523:psychology; D008297:Male; D008425:Maternal Behavior; D012919:Social Behavior; D012931:Social Environment; D059467:Transcriptome