Staphylococcus aureus-derived factors promote Th9 cell polarization and strongly enhance a transcriptional program associated with inflammation and allergy

T helper (Th) 9 cells, characterized by robust secretion of IL-9, have been increasingly associated with allergic disease. However, if and how Th9 cells are modulated by environmental stimuli remains poorly understood. In this study, we show that exposure of CD4 T-cells to Staphylococcus (S.) aureus-derived factors, including its toxins, potently enhances Th9 cell frequency and IL-9 secretion. Furthermore, S. aureus increases the expression of Th9-promoting factors at a transcriptional level, such as FOXO1, miR-155 and TNFRSF4. Addition of retinoic acid (RA) dampens the Th9 responses induced by S. aureus and substantially changes the transcriptional program induced by this bacterium, while also altering the expression of genes associated with allergic inflammation. Together, our results demonstrate a strong influence of microbial and dietary factors on Th9 cell polarization, which may be important in the context of allergy development and treatment. Overall design: Human CD4 T-cells together with autologous monocytes were treated with S.aureus-derived factors, retinoic acid or the combination of the two and then polarized towards Th9 cells. An untreated control was also included. RNA-Seq analysis was performed to investigate the effect of the treatments on Th9 polarization at a transcriptional level.