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. 2017 Dec 22;8:1858. doi: 10.3389/fimmu.2017.01858

Figure 4.

Figure 4

Promyelocytic leukemia zinc finger (PLZF)-driven gene regulatory network directs innate effector function in mouse NKT cells. NKTCR stimulation by self-glycolipid antigen activates downstream nuclear factor of activated T cells (NF-AT), which activates Egr2 gene. Egr2 is essential for Zbtb16 gene expression downstream of NKTCR stimulation. PLZF encoded by Zbtb16 activates T helper (Th) lineage-specific transcription factors, except Tbx21, which codes for the Th1 master regulator Tbet. Promyelocytic leukemia zinc finger (PLZF) also binds to multiple cis-regulatory elements to repress Bach2, which is a repressor of Th cytokine genes. In addition, PLZF binds to cis-regulatory elements of a variety of cytokine and chemokine receptor genes. NF-AT, Tcf3, Tcf12, Egr2, Zbtb16, Bach2, c-Maf, Gata 3, Runx3, Rora, Rorc, Bcl6, and Klf2 encode transcription factors. Other genes under PLZF control encode effector proteins, mostly cytokines (e.g., Il4), cytokine receptor (Il12Rb1, Ifngr1, Il21r), chemockine (Ccr4) or cell adhesins [Cd44, Sell (L-selectin)]. Bach2 represses the induction of T helper (Th) effector cytokine genes. Thick black lines, cis-regulatory elements of genes; solid green lines, enhancer; solid red lines, repressor; dashed green lines, indirect evidence for enhancement; dashed red lines, indirect evidence for repression. Based on Ref. (145, 149, 150, 158).