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|Title:||Transcriptional modulation of the developing immune system by early life social adversity |
|Authors:||Cole, Steven W.|
Arevalo, Jesusa M.
Ruggiero, Angela M.
Heckman, James J.
Suomi, Stephen J.
|Issue Date:||2012 |
|Series/Report no.:||Discussion Paper Series, Forschungsinstitut zur Zukunft der Arbeit 6915|
|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-month-old animals reared under adverse social conditions. Compared to 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 antiviral responses. Promoter-based bioinformatic analyses implicate increased activity of CREB and NF-kB transcription factors and decreased activity of Interferon 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 months 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.|
|Document Type:||Working Paper|
|Appears in Collections:||IZA Discussion Papers, Forschungsinstitut zur Zukunft der Arbeit (IZA)|
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