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

Author

Listed:
  • 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-?B 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.

Suggested Citation

  • Cole, Steven W. & Conti, Gabriella & Arevalo, Jesusa M. & Ruggiero, Angela M. & Heckman, James J. & Suomi, Stephen J., 2012. "Transcriptional Modulation of the Developing Immune System by Early Life Social Adversity," IZA Discussion Papers 6915, Institute of Labor Economics (IZA).
    • Handle: RePEc:iza:izadps:dp6915
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    References listed on IDEAS

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    1. 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 2012-008, Human Capital and Economic Opportunity Working Group.
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    Cited by:

    1. James J. Heckman & Stefano Mosso, 2014. "The Economics of Human Development and Social Mobility," Annual Review of Economics, Annual Reviews, vol. 6(1), pages 689-733, August.
    2. Gabriella Conti & James J. Heckman, 2012. "The Developmental Approach to Child and Adult Health," NBER Working Papers 18664, National Bureau of Economic Research, Inc.
    3. Tiffany C Armenta & Steve W Cole & Daniel H Geschwind & Daniel T Blumstein & Robert K Wayne, 2019. "Gene expression shifts in yellow-bellied marmots prior to natal dispersal," Behavioral Ecology, International Society for Behavioral Ecology, vol. 30(2), pages 267-277.
    4. Simons, Ronald L. & Lei, Man-Kit & Beach, Steven R.H. & Barr, Ashley B. & Cutrona, Carolyn E. & Gibbons, Frederick X. & Philibert, Robert A., 2017. "An index of the ratio of inflammatory to antiviral cell types mediates the effects of social adversity and age on chronic illness," Social Science & Medicine, Elsevier, vol. 185(C), pages 158-165.
    5. Laurens Holmes & Chinacherem Chinaka & Hikma Elmi & Kerti Deepika & Lavisha Pelaez & Michael Enwere & Olumuyiwa T. Akinola & Kirk W. Dabney, 2019. "Implication of Spiritual Network Support System in Epigenomic Modulation and Health Trajectory," IJERPH, MDPI, vol. 16(21), pages 1-17, October.
    6. Marco Francesconi & James J. Heckman, 2016. "Child Development and Parental Investment: Introduction," Economic Journal, Royal Economic Society, vol. 126(596), pages 1-27, October.
    7. Kristen M Brown & Ana V Diez-Roux & Jennifer A Smith & Belinda L Needham & Bhramar Mukherjee & Erin B Ware & Yongmei Liu & Steven W Cole & Teresa E Seeman & Sharon L R Kardia, 2019. "Expression of socially sensitive genes: The multi-ethnic study of atherosclerosis," PLOS ONE, Public Library of Science, vol. 14(4), pages 1-15, April.
    8. Levine, M.E. & Cole, S.W. & Weir, D.R. & Crimmins, E.M., 2015. "Childhood and later life stressors and increased inflammatory gene expression at older ages," Social Science & Medicine, Elsevier, vol. 130(C), pages 16-22.
    9. Francesconi, Marco & Heckman, James J., 2016. "Symposium on Child Development and Parental Investment: Introduction," IZA Discussion Papers 9977, Institute of Labor Economics (IZA).
    10. Francesconi, Marco & Heckman, James J, 2015. "Symposium on Child Development and Parental Investment: Introduction," Economics Discussion Papers 16868, University of Essex, Department of Economics.
    11. Dora L. Costa, 2015. "Health and the Economy in the United States from 1750 to the Present," Journal of Economic Literature, American Economic Association, vol. 53(3), pages 503-570, September.
    12. Gabriella Conti & James J. Heckman, 2012. "The Economics of Child Well-Being," NBER Working Papers 18466, National Bureau of Economic Research, Inc.
    13. Kagawa Singer, M. & Dressler, W. & George, S., 2016. "Culture: The missing link in health research," Social Science & Medicine, Elsevier, vol. 170(C), pages 237-246.

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    More about this item

    Keywords

    primates; development; social adversity; stress; gene expression; immune system;
    All these keywords.

    JEL classification:

    • I12 - Health, Education, and Welfare - - Health - - - Health Behavior
    • J13 - Labor and Demographic Economics - - Demographic Economics - - - Fertility; Family Planning; Child Care; Children; Youth

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