The discovery of transcription factors that are key regulators of the cytokine expression required to launch lineagespecific transcriptional programs has greatly extended our understanding of Th-cell lineage commitment [44] . It has been shown that T-bet and STAT4 program the commitment of the Th1 lineage and Th1 cytokine production [45] , whereas GATA-binding protein 3 (GATA3) and STAT6 drive Th2 population expansion and Th2 cytokine production [46, 47] . The T-bet and STAT4 (necessary for Th1 differentiation) transcription factors are important in the differentiation of autoimmune T cells in the EAE model [48] , and T-betand STAT4-deficient mice are resistant to EAE. However, these transcription factors do not mediate the induction of Th17 cells. Instead, in a unique inductive milieu, Th17 differentiation is driven by distinct transcription factors: retinoic acid receptor-related orphan receptor-γt (Rorγt) and Rorα [33, 34] . Stat3 deletion in T cells also prevents autoimmune uveitis and EAE and increases the expression of IL10 and forkhead box P3 (FoxP3) [49] , and the expression of FoxP3 programs the development and functions of Treg cells [50] . In humans, IL23 and IL1β also induce the development of Th17 cells expressing IL17A, IL17F, IL22, IL26, IFNγ, the chemokine CCL20, and the transcription factor RORγ [51] [52] [53] , as illustrated in Figure 1 (adapted from Hirota et al. [54] ).