1. The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2
- Author
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Scott, Charlotte, Soen, Bieke, Martens, Liesbet, Skrypek, Nicolas, Saelens, Wouter, Taminau, Joachim, Blancke, Gillian, Van Isterdael, Gert, Huylebroeck, Danny, Haigh, Jody, Saeys, Yvan, Guilliams, Martin, Lambrecht, Bart, Berx, Geert, Cell biology, and Pulmonary Medicine
- Subjects
0301 basic medicine ,BONE-MARROW ,Plasma Cells ,Immunology ,FACTOR-BINDING SITES ,CD11c ,macromolecular substances ,Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,TERMINAL DIFFERENTIATION ,Conditional gene knockout ,Medicine and Health Sciences ,Animals ,Immunology and Allergy ,Psychological repression ,Transcription factor ,IN-VIVO ,Research Articles ,SIGNALING CONTROLS ,Inhibitor of Differentiation Protein 2 ,Zinc Finger E-box Binding Homeobox 2 ,Homeodomain Proteins ,Mice, Knockout ,Zinc finger ,urogenital system ,Brief Definitive Report ,hemic and immune systems ,INTESTINAL LAMINA PROPRIA ,Dendritic Cells ,CLONOGENIC PROGENITOR ,Up-Regulation ,3. Good health ,Repressor Proteins ,DENDRITIC CELL-DEVELOPMENT ,030104 developmental biology ,SUBSET DEVELOPMENT ,FACTOR E2-2 ,Cancer research ,IRF8 ,Chromatin immunoprecipitation ,030215 immunology - Abstract
Lambrecht et al. show that the transcription factor Zeb2 regulates commitment toward both the pDC and cDC2 lineages by repressing Id2., Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box–binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c+ cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c+ cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up-regulated in cDC2s and pDCs from conditional knockout mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2.
- Published
- 2016