Aging-dependent upregulation of IL-23p19 gene expression in dendritic cells is associated with differential transcription factor binding and histone modifications

摘要: Age-associated changes in immune response increase the risk of infection and promote inflammation auto-immunity older adults. The newly discovered cytokine IL-23 contributes to maintenance expansion Th-17 cells, which proinflammatory responses. Our preliminary findings suggested that responses are increased aged mice. consists p40 p19 subunits. Expression subunit is regulated at transcriptional level by NF-κB p65 c-Rel transcription factors. Using bone-marrow-derived dendritic cells (DCs) from C57BL/6 mice, we show protein production mRNA levels significantly DCs mice after activation with TLR ligands (LPS + R848) when compared young adult We found expression associated chromatin remodeling characterized di- tri-methylation histone H3K4 binding mainly promoter. In DCs, promoter tri-methylated only bound both c-Rel. C-Rel knockdown restores but does not activate expression, suggesting critical for expression. addition, increases close those detected old cells. Furthermore, decrease was specific gene since IL-12p40 different between DCs. results demonstrate selective methylation, occur contribute upregulation observed This suggests epigenetic mechanisms dysregulated inflammatory autoimmune aging.