Fig. 4. Signalling in T cell lineage commitment. Multiple pathways are implicated in T helper type 2 (Th2) cell differentiation. Importantly, IL4/13 signalling through STAT6 induces the transcription of IL4R and GATA3, which is the master regulator of Th2 differentiation. GATA3, along with other transcription factors, STAT6, STAT5 and c-MAF, induce the transcription of IL4, IL5 and IL13. GATA3 is also activated by the Notch pathway independently of STAT6 activity, providing an explanation for GATA3 expression in Stat6-null mice. The balance between different members of the nuclear factor of activated T-cells (NFAT) family of transcription factors also plays a role in the transcription of IL4 and Th2 differentiation. P, phosphorylation; TACE (ADAM17); ICD, intracellular domain.