Interactions among the transcription factors Runx1, RORγt and Foxp3 regulate the differentiation of interleukin 17-producing T cells

The molecular mechanisms underlying the differentiation of interleukin 17-producing T helper cells (T-H-17 cells) are still poorly understood. Here we show that optimal transcription of the gene encoding interleukin 17 (Il17) required a 2-kilobase promoter and at least one conserved noncoding (enhancer) sequence, CNS-5. Both cis-regulatory elements contained regions that bound the transcription factors ROR gamma t and Runx1. Runx1 influenced T-H-17 differentiation by inducing ROR gamma t expression and by binding to and acting together with ROR gamma t during Il17 transcription. However, Runx1 also interacts with the transcription factor Foxp3, and this interaction was necessary for the negative effect of Foxp3 on T-H-17 differentiation. Thus, our data support a model in which the differential association of Runx1 with Foxp3 and with ROR gamma t regulates T-H-17 differentiation.