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Transcriptional Modulation of the Developing Immune System by Early Life Social Adversity

  • Cole, Steven W.

    ()

    (University of California, Los Angeles)

  • Conti, Gabriella

    ()

    (University College London)

  • Arevalo, Jesusa M.

    (University of California, Los Angeles)

  • Ruggiero, Angela M.

    ()

    (NICHD)

  • Heckman, James J.

    ()

    (University of Chicago)

  • Suomi, Stephen J.

    ()

    (NICHD)

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-κB 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.

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Paper provided by Institute for the Study of Labor (IZA) in its series IZA Discussion Papers with number 6915.

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Length: 24 pages
Date of creation: Oct 2012
Date of revision:
Publication status: published in: Proceedings of the National Academy of Sciences, 2012, 109(50), 20578-20583
Handle: RePEc:iza:izadps:dp6915
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  1. Lex Borghans & Angela Lee Duckworth & James J. Heckman & Bas ter Weel, 2008. "The Economics and Psychology of Personality Traits," NBER Working Papers 13810, National Bureau of Economic Research, Inc.
  2. James J. Heckman & Seong Hyeok Moon & Rodrigo Pinto & Peter A. Savelyev & Adam Yavitz, 2010. "Analyzing Social Experiments as Implemented: A Reexamination of the Evidence From the HighScope Perry Preschool Program," NBER Working Papers 16238, National Bureau of Economic Research, Inc.
  3. Flavio Cunha & James Heckman & Susanne Schennach, 2010. "Estimating the technology of cognitive and noncognitive skill formation," CeMMAP working papers CWP09/10, Centre for Microdata Methods and Practice, Institute for Fiscal Studies.
  4. Conti, Gabriella & Hansman, Christopher & Heckman, James J. & Novak, Matthew F.X. & Ruggiero, Angela M. & Suomi, Stephen J., 2012. "Primate Evidence on the Late Health Effects of Early Life Adversity," IZA Discussion Papers 6495, Institute for the Study of Labor (IZA).
  5. Joseph Romano & Michael Wolf, 2003. "Exact and approximate stepdown methods for multiple hypothesis testing," Economics Working Papers 727, Department of Economics and Business, Universitat Pompeu Fabra.
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