Journal article

Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT

Michael Chopin, Aaron T Lun, Yifan Zhan, Jaring Schreuder, Hannah Coughlan, Angela D'Amico, Lisa A Mielke, Francisca F Almeida, Andrew J Kueh, Ross A Dickins, Gabrielle T Belz, Shalin H Naik, Andrew M Lew, Phillipe Bouillet, Marco J Herold, Gordon K Smyth, Lynn M Corcoran, Stephen L Nutt

IMMUNITY | CELL PRESS | Published : 2019

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 mai..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Victorian Cancer Agency


Funding Acknowledgements

We thank S. O'Connor, T. Kratina, T. Camilleri, A. Hilton, and A. Jarratt for excellent technical assistance and A. Stock for comments on the manuscript draft. This work benefitted from data assembled by the ImmGen consortium. This research was supported by the National Health and Medical Research Council of Australia (5575500, 1054925, and 1048278 to S.L.N.; 1054618 and 1058892 to G.K.S.; 1037321, 1043414, 1080321, and 1105209 to A.M.L.) and the Cancer Council Victoria Venture Grant and Victorian Cancer Agency (TRP13041 to M.J.H.). This work was made possible through support from the Australian Phenomics Network.