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Modulation of immune cell function by an early life experience (167.11)

Susan Smith, Lauren Williamson, Paige Sholar and Staci Bilbo
J Immunol May 1, 2012, 188 (1 Supplement) 167.11;
Susan Smith
1Department of Psychology and Neuroscience, Duke University, Durham, NC
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Lauren Williamson
1Department of Psychology and Neuroscience, Duke University, Durham, NC
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Paige Sholar
1Department of Psychology and Neuroscience, Duke University, Durham, NC
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Staci Bilbo
1Department of Psychology and Neuroscience, Duke University, Durham, NC
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Abstract

Pro-inflammatory IL-1 beta cytokine production within the hippocampus (HP) is required for normal learning. However, excessive IL-1 beta levels in the brain can interfere with memory consolidation, resulting in cognitive deficits and neurodegeneration. We have identified the cellular source of IL-1 beta during learning as microglia, a CNS-resident macrophage cell type. Intriguingly, microglia from adult rats that suffered an immune challenge early in life are “primed” for exaggerated IL-1 beta responses, which is maladaptive because it can interfere with normal learning and memory. Similar to control cells, primed microglia do not produce cytokines constitutively. Rather, exaggerated cytokine responses in primed microglia likely result from an altered pattern of transcriptional regulation that was initiated during an early life infection and is propagated into adulthood via specific epigenetic markings. We have found that HP microglia from neonatally infected rats have a global reduction in dimethylated histone H3K9 compared to control (mock-infected) rats. The specific gene loci involved in the regulation of microglial cytokine expression from primed and control rats are now under investigation. Thus, our model of early life infection demonstrates a role for brain-resident immune cells in mediating the “programming” of a later cognitive dysfunction via intrinsic differences in their epigenetic status.

  • Copyright © 2012 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 188, Issue 1 Supplement
May 2012
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Modulation of immune cell function by an early life experience (167.11)
Susan Smith, Lauren Williamson, Paige Sholar, Staci Bilbo
The Journal of Immunology May 1, 2012, 188 (1 Supplement) 167.11;

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Modulation of immune cell function by an early life experience (167.11)
Susan Smith, Lauren Williamson, Paige Sholar, Staci Bilbo
The Journal of Immunology May 1, 2012, 188 (1 Supplement) 167.11;
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Print ISSN 0022-1767        Online ISSN 1550-6606