Attenuate ICOSL and IL-27 in Aire-overexpressing DC2.4 cells suppress TFH cell differentiation

Autoimmune regulator (Aire) is a transcription factor that plays a pivotal role in the maintenance of immune tolerance. However, little is known about its roles in peripheral immune tolerance. Aire is predominantly expressed in dendritic cells (DCs) in the periphery. DCs with higher inducible costimulatory ligand (ICOSL) expression and interleukin (IL)-27 production have been reported highly suggesting its roles in inducing follicular helper T cells (TFH). Here we use Aire-overexpressing DC2.4 cells in a coculture system composed of naïve CD4+ T cells to test whether Aire in DCs affects TFH cell differentiation. We found that the frequency of TFH cells and its specific cytokine IL-21 were decreased in CD4+ T lymphocytes after cocultured with Aire overexpressed DC2.4 cells. In activated DCs, ICOSL expression and IL-27 production were significantly suppressed by Aire. Furthermore, addition of recombinant ICOSL or IL-27 in the coculture system enhanced TFH cell differentiation and IL-21 expression. These results revealed that Aire plays an indispensable role in the repression of dendritic cells on the differentiation and function of TFH cells by inhibiting ICOSL and IL-27 expression.