Figure 4. Transcription factor networks that underlie the differentiation of peripheral naive CD4⁺ T cells into T-helper- and regulatory T-cell subsets.

RUNX3 (runt-related transcription factor 3) represses the production of interleukin-4 (IL-4) by binding to the Il4 silencer in the T helper 2 (T_H2) cytokine locus while cooperating with T-bet to promote the production of interferon-γ (IFNγ) in T_H1 cells. GATA-binding protein 3 (GATA3), which is required for the expression of T_H2-type cytokines (encoded by the T_H2-cytokine locus), represses the expression of the T_H1-cell-associated gene Il12rb2 in T_H2 cells. In T_H17 cells, RUNX1 cooperates with the transcription factor retinoic-acid-receptor-related orphan receptor-γt (RORγt) to induce the production of IL-17. In regulatory T (T_Reg) cells, forkhead box P3 (FOXP3) represses the RUNX1-mediated production of IL-2.