T helper 9 (Th9) cellular proliferation and cytokine production is regulated by cAMP responsive element modulator (Crem) (HYP7P.289)

Abstract

Abstract Th9 cells, a CD4+ T cell subset characterized by their robust production of interleukin (IL)-9, can promote allergic inflammation in mice and are associated with atopic disease in humans. Because it might provide targets for therapeutic intervention, it is important to understand the molecular controls governing overall Th9 development and their subsequent effector function. To understand the Th9 transcriptional profile, we recently performed microarray analysis to highlight gene expression enriched in Th9 cells compared to other Th subsets. Crem, which expresses a basic leucine zip domain protein with roles in activating and repressing genes, was among a number of genes with increased expression in Th9 cells. Analysis of mRNA and protein expression among in vitro differentiated Th subsets confirmed Crem was enriched in Th9 cells compared to other subsets. Interestingly, ectopic expression of Crem in Th9 cells repressed their capacity to produce IL-9 upon CD3 re-stimulation while promoting overall cellular proliferation. Crem ectopic expression also promoted cellular expansion in other cultured Th subsets. Conversely, acute siRNA knockdown of Crem mRNA in Th9 differentiated cells resulted in reduced cellular proliferation and enhanced IL-9 production upon CD3 restimulation. Therefore, Crem potentially serves a role in modifying Th9 effector activities upon T cell receptor signaling during allergic disease.