Schematic of the NFAT interaction partners in Th17 cells. Th17 differentiation is initiated by TCR-derived signals in combination with the activation of the IL-6R via IL-6 and the TGF-β signaling cascade (via the TGF-βR). STAT3 activated via the IL-6R together with NFAT and AP-1, binds to the promoter of RORγt, which is the master transcription factor of the Th17 lineage. Subsequently, RORγt, in combination with NFAT, AP-1, STAT3, AhR, IRF4, and Runx1, binds to the Il17 promoter region to induce transcription. In parallel, NFAT, together with STAT3 and c-MAF, activates the transcription of Il21 and, in combination with RORγt and AhR, the transcription of Il22. IL-21 and low concentrations of TGF-β (via Smad2/3) induce the expression of the IL-23R components (not shown); subsequently, NFAT, IRF4, and Smad2/3 drive the transcription of Il23.