Journal
EXPERIMENTAL GERONTOLOGY
Volume 45, Issue 11, Pages 834-841Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2010.06.007
Keywords
Aging; Dendritic cells; T helper cells; IL 23; PGE2; Th17
Categories
Funding
- National Institutes of Health (NIAID) [AI057952]
- National Institutes on Aging (NIA) [R21/AG 003382501]
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CD4+ T cells of the Th17 subtype are over-represented in the aged immune system Dendritic cells (DC) play a critical role in naive CD4+ T cell differentiation However expression of cytokines by aged DC that promote differentiation or survival of Th17 cells has not been extensively investigated Using bone marrow-derived DC from C57BL/6 mice of different ages we compared cytokine production after DC activation by Toll like receptor agonists for TLR4 and/or TLR7/8 DC-derived TNF-alpha and IL 12p70 production and expression of DC co-stimulatory molecules did not vary significantly by age indicating that TLR expression function and signal transduction were Intact in aged DC There were relatively minor age-related changes in TGF-beta and IL-6 which promote Th17 differentiation but IL-23 a Th17-suvival cytokine increased more than 40-fold across the lifespan DC-derived prostaglandin E2 (PGE2) also increased with age and the up-regulation of IL-23 expression by aged DC was blocked by indomethacin that prevents PGE2 production and by antagonists of PGE2 receptors Exogenous PGE2 added to DC cultures further enhanced IL 23 production from aged but not young DCs These data indicate that age related changes in DC PGE2 production are necessary but not sufficient to Induce DC IL-23 production Such changes may play a role in the expansion of Th17 cells in the aged Immune system (C) 2010 Elsevier Inc All rights reserved
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