Impaired interleukin-12-dependent T-cell functions during aging: role of signal transducer and activator of transcription 4 (STAT4) and suppressor of cytokine signaling 3 (SOCS3)
Abstract
Interleukin (IL)-12 is the major inducer of T helper cell (Th) 1-type responses. Despite a higher IL-12 production, phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC), as well as CD4(+) or CD8(+) T cells from elderly donors released interferon (IFN)-gamma amounts similar to those observed in young controls, and underwent only a slight increase in IFN-gamma production after IL-12 costimulation. These findings were not due to an age-related reduction in IL-12 receptor expression. Interestingly, no difference in PHA-triggered signal transducer and activator of transcription 4 (STAT4) phosphorylation between young and elderly donors was found, and a significant IL-12-induced STAT4 activation occurred only in PHA-preactivated cells from the younger group. The age-related defect in IL-12 signaling was STAT4-restricted as it did not involve the p38 mitogen-activated protein kinase (MAPK) pathway. Finally, suppressor of cytokine signaling 3 (SOCS3) expression was significantly higher in unstimulated cells from elderly individuals, and it did not diminish after cell stimulation. These results indicate that a defective STAT4 activation, likely dependent on elevated SOCS3 levels, is involved in the impaired IL-1...Continue Reading
References
A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits
Citations
Interleukin-2, interleukin-12, and interferon-gamma levels and risk of young adult Hodgkin lymphoma.
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Aging Genetics (Keystone)
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