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

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Author Info

  • 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)

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-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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Bibliographic Info

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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Related research

Keywords: immune system; gene expression; stress; social adversity; development; primates;

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References

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  1. Borghans Lex & Lee Duckworth Angela & Heckman James J. & Weel Bas ter, 2008. "The Economics and Psychology of Personality Traits," ROA Research Memorandum 001, Maastricht University, Research Centre for Education and the Labour Market (ROA).
  2. Gabriella Conti & Christopher Hansman & James J. Heckman & Matthew F. X. Novak & Angela Ruggiero & Stephen J. Suomi, 2012. "Primate Evidence on the Late Health Effects of Early Life Adversity," Working Papers, Human Capital and Economic Opportunity Working Group 2012-008, Human Capital and Economic Opportunity Working Group.
  3. 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," Working Papers, Geary Institute, University College Dublin 201034, Geary Institute, University College Dublin.
  4. Joseph P. Romano & Michael Wolf, 2005. "Exact and Approximate Stepdown Methods for Multiple Hypothesis Testing," Journal of the American Statistical Association, American Statistical Association, American Statistical Association, vol. 100, pages 94-108, March.
  5. Flavio Cunha & James J. Heckman & Susanne M. Schennach, 2010. "Estimating the Technology of Cognitive and Noncognitive Skill Formation," Econometrica, Econometric Society, Econometric Society, vol. 78(3), pages 883-931, 05.
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Cited by:
  1. Conti, Gabriella & Heckman, James J., 2012. "The Economics of Child Well-Being," IZA Discussion Papers 6930, Institute for the Study of Labor (IZA).
  2. Dora Costa, 2013. "Health and the Economy in the United States, from 1750 to the Present," NBER Working Papers 19685, National Bureau of Economic Research, Inc.
  3. James J. Heckman & Stefano Mosso, 2014. "The Economics of Human Development and Social Mobility," Annual Review of Economics, Annual Reviews, Annual Reviews, vol. 6(1), pages 689-733, 08.
  4. Gabriella Conti & James J. Heckman, 2012. "The Developmental Approach to Child and Adult Health," NBER Working Papers 18664, National Bureau of Economic Research, Inc.

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