The Nrf2 activator tBHQ inhibits dendritic cell maturation and activation in response to bacterial and viral stimuli

Dendritic cells (DCs) are professional antigen presenting cells that promote both innate and adaptive immune responses. Pertinent to adaptive immunity, DCs activate naïve T cells by presenting peptides on MHC class II molecules. Tert-butylhydroquinone (tBHQ) is a widely used food additive and a potent activator of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Studies from our lab demonstrated that tBHQ impedes CD4 and CD8 T cell activation and effector function, but the effects of tBHQ on dendritic cell function remain unclear. To address this, splenic DCs were collected from wildtype C57BL/6 mice and treated with tBHQ (0.5 or 1 μM) for 30 mins prior to activation with either LPS or influenza A virus for 24 h. tBHQ treatment led to a significant decrease in the expression of the MHC class II receptor, CD80 and CD86, suggesting tBHQ may negatively impact DC maturation and activation. In addition, tBHQ inhibited secretion of IL-6, and to a lesser extent, TNFα, by LPS and IAV-activated DCs. Overall, our data suggest that tBHQ inhibits the expression of proteins important for DC function, which could ultimately have a negative impact on T cell response to pathogen.