Autoimmune regulator-overexpressing dendritic cells induce T helper 1 and T helper 17 cells by upregulating cytokine expression

摘要

The autoimmune regulator (Aire) protein is a transcriptional activator that is essential in central immune tolerance, as it regulates the ectopic expression of many tissue-restricted antigens in medullary thymic epithelial cells. Aire expression has also been described in hematopoietic cells, such as monocytes/macrophages and dendritic cells (DCs), in the peripheral immune system. However, the role of Aire expression in peripheral immune system cells, including DCs, remains to be elucidated. In the present study, the effects of secreted cytokines from Aire-overexpressing DCs on cluster of differentiation (CD)4(+) T cell subsets were investigated. The dendritic cell line, DC2.4, which overexpresses Aire, was co-cultured with CD4(+) T cells from splenocytes using Transwell inserts. The results indicate that Aire-overexpressing cells induce T helper (Th)1 subsets by increasing interleukin (IL)-12 expression, and induce Th17 subsets by upregulating IL-6 and transforming growth factor (TGF)-beta production. In addition, it was observed that increased levels of phosphorylated extracellular signal-regulated kinases and p38 upregulated the expression of cytokines in Aire-overexpressing cells. These data suggest that Aire may have a role in inducing Th1 and Th17 differentiation by upregulating cytokine expression in DCs.