@article{dcc1074a54794c4b8b9f69ce7fcd516a,
title = "Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT",
abstract = "The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of DC lineage diversity, its genetic basis is not fully understood. The transcription factor DC-SCRIPT is expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8 (interferon regulatory factor 8)-dependent cDC1, whereas cDC2 numbers increased marginally. The residual DC-SCRIPT-deficient cDC1s had impaired capacity to capture and present cell-associated antigens and to secrete IL-12p40, two functional hallmarks of this population. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8. Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.",
author = "Shengbo Zhang and Coughlan, {Hannah D.} and Mitra Ashayeripanah and Simona Seizova and Kueh, {Andrew J.} and Brown, {Daniel V.} and Wang Cao and Nicolas Jacquelot and Angela D'Amico and Lew, {Andrew M.} and Yifan Zhan and Tonkin, {Christopher J.} and Villadangos, {Jose A.} and Smyth, {Gordon K.} and Micha{\"e}l Chopin and Nutt, {Stephen L.}",
note = "Funding Information: This work was supported by the National Health and Medical Research Council of Australia [1155342 and 1054925 (S.L.N.); 1143976, 1150425, and 1080321 (A.M.L.); 1058892 (G.K.S.); and 1154502, 1113293, and 1163090 (J.A.V.)] and the Melbourne research scholarship (S.Z.). M.C. is supported by the Jenny Thatchell/Pauline Speedy and the Barbara McDonald Innovation grants, H.D.C. by the Marian and E.H. Flack Fellowship, and H.D.C. and G.K.S. by the Chan Zuckerberg Initiative EOSS program. This work was made possible through the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS. The generation of the Zfp366−/− and Zfp366-tdTomato mice used in this study was supported by the Australian Phenomics Network (APN) and the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program. Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works",
year = "2021",
month = apr,
doi = "10.1126/sciimmunol.abf4432",
language = "English",
volume = "6",
journal = "Science Immunology",
issn = "2470-9468",
publisher = "American Association for the Advancement of Science (AAAS)",
number = "58",
}