Review Article

Dendritic Cell Development: A Choose-Your-Own-Adventure Story

Figure 1

Gene regulatory networks for cDC and pDC development. Shared gene regulation patterns in (a) and (b). upregulates many factors important for DC development, including Id2, GM-CSFR, and Flt3L [26, 27]. The Flt3 pathway phosphorylates STAT3, which can upregulate/downregulate target genes [28]. (a) Gene regulation in cDCs. Id2 expression inhibits E2-2 via protein interaction. GM-CSFR phosphorylates STAT5, which can inhibit IRF-8 expression [29]. Batf3 upregulates E4BP4 [30]. Batf expression in CD8+ cDCs compensates for a lack of Batf3 [31]. E4BP4 negatively modulates IRF-4 expression [30]. (b) Gene regulation in pDCs. Ikaros upregulates Gfi1 [32], which can inhibit Id2 expression [33], allowing for E2-2 function. E2-2 binds to the promoter of Spi-B, IRF-7, and IRF-8 to upregulate gene expression [34]. A yet unidentified mechanism prevents the downstream events of GM-CSFR in pDCs, since STAT5 has been shown to downregulate IRF-8, which is required for pDC development. Proven interactions are indicated in solid bars. Hypothesized interactions are shown in dashed lines.
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(a)
949513.fig.001b
(b)