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

24 Pages Posted: 20 Oct 2012

See all articles by Steven Cole

Steven Cole

University of California, Los Angeles (UCLA)

Gabriella Conti

University of Chicago

Jesusa Arevalo

affiliation not provided to SSRN

Angela Ruggiero

NICHD

James J. Heckman

University of Chicago - Department of Economics; National Bureau of Economic Research (NBER); American Bar Foundation; Institute for the Study of Labor (IZA); CESifo (Center for Economic Studies and Ifo Institute)

Stephen Suomi

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.

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

JEL Classification: I12, J13

Suggested Citation

Cole, Steven and Conti, Gabriella and Arevalo, Jesusa and Ruggiero, Angela and Heckman, James J. and Suomi, Stephen, Transcriptional Modulation of the Developing Immune System by Early Life Social Adversity. IZA Discussion Paper No. 6915, Available at SSRN: https://ssrn.com/abstract=2164644 or http://dx.doi.org/10.2139/ssrn.2164644

Steven Cole

University of California, Los Angeles (UCLA) ( email )

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Gabriella Conti

University of Chicago ( email )

1101 East 58th Street
Chicago, IL 60637
United States

Jesusa Arevalo

affiliation not provided to SSRN

No Address Available

Angela Ruggiero

NICHD ( email )

31 Center Drive
Building 31, Room 2A32
Bethesda, MD 20892-2425
United States

James J. Heckman

University of Chicago - Department of Economics ( email )

1126 East 59th Street
Chicago, IL 60637
United States
773-702-0634 (Phone)
773-702-8490 (Fax)

National Bureau of Economic Research (NBER)

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Cambridge, MA 02138
United States

American Bar Foundation

750 N. Lake Shore Drive
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United States

Institute for the Study of Labor (IZA)

P.O. Box 7240
Bonn, D-53072
Germany

CESifo (Center for Economic Studies and Ifo Institute)

Poschinger Str. 5
Munich, DE-81679
Germany

Stephen Suomi

NICHD ( email )

31 Center Drive
Building 31, Room 2A32
Bethesda, MD 20892-2425
United States

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