Schematic of the NFAT interaction partners in Th2 cells. Th2 lineage is initiated by TCR and costimulatory signals, as well as the Th2 determining factor IL-4. IL-4 via the IL-4R together with IL-2 (via the IL-2R) and the Notch1/2/RBPJ/MAML1 signaling pathway activates the master transcription factor of the Th2 lineage, GATA3. GATA3, together with NFAT, NF-κB, AP-1, IRF4, c-MAF, STAT5, STAT6, BRG1, and RBPJ, binds the Il4 promoter region. GATA3 subsequently enhances, in combination with NFAT and GIF, the transcription of Il4, Il5, and Il13 via a positive feedback loop. GATA3 also induces the transcription of c-Maf. NFAT, in parallel with IRF4, binds the Il10 promoter and induces Il10 expression. NFAT and Runx inhibit Th2 differentiation.