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

Michaël 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

doi:10.1016/j.immuni.2018.11.010

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

Michaël 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

Australian Centre for Blood Diseases

Research output: Contribution to journal › Article › Research › peer-review

65 Citations (Scopus)

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.

Original language	English
Pages (from-to)	77-90.e5
Number of pages	19
Journal	Immunity
Volume	50
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2018.11.010
Publication status	Published - 15 Jan 2019

Keywords

cell differentiation
DC-SCRIPT
dendritic cell
plasmacytoid dendritic cell
PU.1
transcription factor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2018.11.010

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Chopin, M., Lun, A. T., Zhan, Y., Schreuder, J., Coughlan, H., D'Amico, A., Mielke, L. A., Almeida, F. F., Kueh, A. J., Dickins, R. A., Belz, G. T., Naik, S. H., Lew, A. M., Bouillet, P., Herold, M. J., Smyth, G. K., Corcoran, L. M., & Nutt, S. L. (2019). Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT. Immunity, 50(1), 77-90.e5. https://doi.org/10.1016/j.immuni.2018.11.010

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

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.",

keywords = "cell differentiation, DC-SCRIPT, dendritic cell, plasmacytoid dendritic cell, PU.1, transcription factor",

author = "Micha{\"e}l Chopin and Lun, {Aaron T.} and Yifan Zhan and Jaring Schreuder and Hannah Coughlan and Angela D'Amico and Mielke, {Lisa A.} and Almeida, {Francisca F.} and Kueh, {Andrew J.} and Dickins, {Ross A.} and Belz, {Gabrielle T.} and Naik, {Shalin H.} and Lew, {Andrew M.} and Phillipe Bouillet and Herold, {Marco J.} and Smyth, {Gordon K.} and Corcoran, {Lynn M.} and Nutt, {Stephen L.}",

year = "2019",

month = jan,

day = "15",

doi = "10.1016/j.immuni.2018.11.010",

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Chopin, M, Lun, AT, Zhan, Y, Schreuder, J, Coughlan, H, D'Amico, A, Mielke, LA, Almeida, FF, Kueh, AJ, Dickins, RA, Belz, GT, Naik, SH, Lew, AM, Bouillet, P, Herold, MJ, Smyth, GK, Corcoran, LM & Nutt, SL 2019, 'Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT', Immunity, vol. 50, no. 1, pp. 77-90.e5. https://doi.org/10.1016/j.immuni.2018.11.010

TY - JOUR

T1 - Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT

AU - Chopin, Michaël

AU - Lun, Aaron T.

AU - Zhan, Yifan

AU - Schreuder, Jaring

AU - Coughlan, Hannah

AU - D'Amico, Angela

AU - Mielke, Lisa A.

AU - Almeida, Francisca F.

AU - Kueh, Andrew J.

AU - Dickins, Ross A.

AU - Belz, Gabrielle T.

AU - Naik, Shalin H.

AU - Lew, Andrew M.

AU - Bouillet, Phillipe

AU - Herold, Marco J.

AU - Smyth, Gordon K.

AU - Corcoran, Lynn M.

AU - Nutt, Stephen L.

PY - 2019/1/15

Y1 - 2019/1/15

N2 - 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.

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.

KW - cell differentiation

KW - DC-SCRIPT

KW - dendritic cell

KW - plasmacytoid dendritic cell

KW - PU.1

KW - transcription factor

UR - http://www.scopus.com/inward/record.url?scp=85060056317&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2018.11.010

DO - 10.1016/j.immuni.2018.11.010

M3 - Article

C2 - 30611612

AN - SCOPUS:85060056317

SN - 1074-7613

VL - 50

SP - 77-90.e5

JO - Immunity

JF - Immunity

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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