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Title: Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT.
Austin Authors: Chopin, Michaël;Lun, Aaron T;Zhan, Yifan;Schreuder, Jaring;Coughlan, Hannah;D'Amico, Angela;Mielke, Lisa A;Almeida, Francisca F;Kueh, Andrew J;Dickins, Ross A;Belz, Gabrielle T;Naik, Shalin H;Lew, Andrew M;Bouillet, Phillipe;Herold, Marco J;Smyth, Gordon K;Corcoran, Lynn M;Nutt, Stephen L
Affiliation: Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia
Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC 3010, Australia
Issue Date: 15-Jan-2019 2019-01-15
Publication information: Immunity 2019; 50(1): 77-90.e5
Abstract: Dendritic cells (DCs) are can be broadly divided into conventional (cDC) and plasmacytoid (pDC) subsets. Despite the importance of this lineage diversity, its genetic basis is not fully understood. We found that conditional ablation of the Ets-family transcription factor PU.1 in DC-restricted progenitors led to increased pDC production at the expense of cDCs. PU.1 controlled many of the cardinal functions of DCs, such as antigen presentation by cDCs and type I interferon production by pDCs. Conditional ablation of PU.1 de-repressed the pDC transcriptional signature in cDCs. The combination of genome-wide mapping of PU.1 binding and gene expression analysis revealed a key role for PU.1 in maintaining cDC identity through the induction of the transcriptional regulator DC-SCRIPT. PU.1 activated DC-SCRIPT expression, which in turn promoted cDC formation, particularly of cDC1s, and repressed pDC development. Thus, cDC identity is regulated by a transcriptional node requiring PU.1 and DC-SCRIPT.
DOI: 10.1016/j.immuni.2018.11.010
Journal: Immunity
PubMed URL: 30611612
Type: Journal Article
Subjects: DC-SCRIPT
cell differentiation
dendritic cell
plasmacytoid dendritic cell
transcription factor
Appears in Collections:Journal articles

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