Prostaglandin E2-dependent IL-23 production in aged murine dendritic cells.
CD4+ T cells of the Th17 subtype are over-represented in the aged immune system. Dendritic cells (DC) play a critical role in naïve 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-α 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-β 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.
Myer
Rebecca G
RG
Department of Internal Medicine, Section of Infectious Diseases, Wake Forest University School of Medicine, 100 Medical Center Blvd., Winston-Salem, NC 27157, USA.
El Mezayen
Rabab
R
High
Kevin P
KP
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D053759:Interleukin-23 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D015398:Signal Transduction; D058504:Th17 Cells / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000819:agonists; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051200:Toll-Like Receptor 8 / Q000819:agonists; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; D053759:Interleukin-23; D015850:Interleukin-6; D018078:Receptors, Prostaglandin E; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D016212:Transforming Growth Factor beta; D015232:Dinoprostone