PMID- 30611612 OWN - NLM STAT- MEDLINE DCOM- 20190705 LR - 20190705 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 50 IP - 1 DP - 2019 Jan 15 TI - Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT. PG - 77-90.e5 LID - S1074-7613(18)30492-8 [pii] LID - 10.1016/j.immuni.2018.11.010 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Chopin, Michael AU - Chopin M AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: chopin@wehi.edu.au. FAU - Lun, Aaron T AU - Lun AT AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Zhan, Yifan AU - Zhan Y AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Schreuder, Jaring AU - Schreuder J AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Coughlan, Hannah AU - Coughlan H AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - D'Amico, Angela AU - D'Amico A AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Mielke, Lisa A AU - Mielke LA AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, VIC 3084, Australia. FAU - Almeida, Francisca F AU - Almeida FF AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Kueh, Andrew J AU - Kueh AJ AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Dickins, Ross A AU - Dickins RA AD - Australian Centre for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia. FAU - Belz, Gabrielle T AU - Belz GT AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Naik, Shalin H AU - Naik SH AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Lew, Andrew M AU - Lew AM AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Bouillet, Phillipe AU - Bouillet P AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Herold, Marco J AU - Herold MJ AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Smyth, Gordon K AU - Smyth GK AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Corcoran, Lynn M AU - Corcoran LM AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Nutt, Stephen L AU - Nutt SL AD - Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: nutt@wehi.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190102 PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (DC-SCRIPT protein, mouse) RN - 0 (DNA-Binding Proteins) RN - 0 (Interferon Type I) RN - 0 (Nuclear Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 0 (proto-oncogene protein Spi-1) SB - IM MH - Animals MH - Antigen Presentation MH - Cell Differentiation MH - Cell Lineage MH - DNA-Binding Proteins/genetics/*metabolism MH - Dendritic Cells/*physiology MH - Gene Expression Regulation MH - HEK293 Cells MH - Humans MH - Interferon Type I/metabolism MH - Mice MH - Mice, Transgenic MH - Nuclear Proteins/genetics/*metabolism MH - Proto-Oncogene Proteins/genetics/*metabolism MH - Signal Transduction MH - Trans-Activators/genetics/*metabolism MH - Transcription Factors/genetics/*metabolism MH - Transcriptome OTO - NOTNLM OT - DC-SCRIPT OT - PU.1 OT - cell differentiation OT - dendritic cell OT - plasmacytoid dendritic cell OT - transcription factor EDAT- 2019/01/07 06:00 MHDA- 2019/07/06 06:00 CRDT- 2019/01/07 06:00 PHST- 2017/07/24 00:00 [received] PHST- 2018/09/20 00:00 [revised] PHST- 2018/11/02 00:00 [accepted] PHST- 2019/01/07 06:00 [pubmed] PHST- 2019/07/06 06:00 [medline] PHST- 2019/01/07 06:00 [entrez] AID - S1074-7613(18)30492-8 [pii] AID - 10.1016/j.immuni.2018.11.010 [doi] PST - ppublish SO - Immunity. 2019 Jan 15;50(1):77-90.e5. doi: 10.1016/j.immuni.2018.11.010. Epub 2019 Jan 2.