文章基本信息

标题：Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate
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作者：Xiaodi Wu ; Carlos G. Briseño ; Gary E. Grajales-Reyes 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：51
页码：14775-14780
DOI：10.1073/pnas.1611408114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceDistinct transcription factors regulate the development of immune cell lineages, and changes in their expression can alter the balance of cell types responding to infection. Recent studies have identified Zeb2 as a transcription factor important for the final maturation of natural killer cells and effector CD8+ T cells. In this study, we show that Zeb2 is required for the development of two myeloid cell types, the monocyte and the plasmacytoid dendritic cell, and clarify that this factor is not required for the development of classical dendritic cells. Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6Chi monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.
关键词：monocyte ; plasmacytoid dendritic cell ; transcription factor