IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

Dorine Sichien; Charlotte L Scott; Liesbet Martens; Matthias Vanderkerken; Sofie Van Gassen; Maud Plantinga; Thorsten Joeris; Sofie De Prijck; Leen Vanhoutte; Manon Vanheerswynghels; Gert Van Isterdael; Wendy Toussaint; Filipe Branco Madeira; Karl Vergote; William Winston Agace; Björn E. Clausen; Hamida Hammad; Marc Dalod; Yvan Saeys; Bart N. Lambrecht; Martin Guilliams

doi:10.1016/j.immuni.2016.08.013

IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

Dorine Sichien, Charlotte L Scott, Liesbet Martens, Matthias Vanderkerken, Sofie Van Gassen, Maud Plantinga, Thorsten Joeris, Sofie De Prijck, Leen Vanhoutte, Manon Vanheerswynghels, Gert Van Isterdael, Wendy Toussaint, Filipe Branco Madeira, Karl Vergote, William Winston Agace, Björn E. Clausen, Hamida Hammad, Marc Dalod, Yvan Saeys, Bart N. LambrechtMartin Guilliams

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the identity of terminally differentiated cells are designated "terminal selectors." Using BM chimeras, conditional Irf8(fl/fl) mice and various promotors to target Cre recombinase to different stages of monocyte and DC development, we have identified IRF8 as a terminal selector of the cDC1 lineage controlling survival. In monocytes, IRF8 was necessary during early but not late development. Complete or late deletion of IRF8 had no effect on pDC development or survival but altered their phenotype and gene-expression profile leading to increased T cell stimulatory function but decreased type 1 interferon production. Thus, IRF8 differentially controls the survival and function of terminally differentiated monocytes, cDC1s, and pDCs.

Original language	English
Journal	Immunity
Volume	45
Issue number	3
Pages (from-to)	626-640
Number of pages	15
ISSN	1074-7613
DOIs	https://doi.org/10.1016/j.immuni.2016.08.013
Publication status	Published - 2016

Keywords

IRF4
IRF8
dendritic cell
development
lineage
monocyte
plasmacytoid dendritic cell
terminal selector
transcription factor

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Sichien, D., Scott, C. L., Martens, L., Vanderkerken, M., Van Gassen, S., Plantinga, M., Joeris, T., De Prijck, S., Vanhoutte, L., Vanheerswynghels, M., Van Isterdael, G., Toussaint, W., Madeira, F. B., Vergote, K., Agace, W. W., Clausen, B. E., Hammad, H., Dalod, M., Saeys, Y., ... Guilliams, M. (2016). IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively. Immunity, 45(3), 626-640. https://doi.org/10.1016/j.immuni.2016.08.013

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title = "IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively",

abstract = "Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the identity of terminally differentiated cells are designated {"}terminal selectors.{"} Using BM chimeras, conditional Irf8(fl/fl) mice and various promotors to target Cre recombinase to different stages of monocyte and DC development, we have identified IRF8 as a terminal selector of the cDC1 lineage controlling survival. In monocytes, IRF8 was necessary during early but not late development. Complete or late deletion of IRF8 had no effect on pDC development or survival but altered their phenotype and gene-expression profile leading to increased T cell stimulatory function but decreased type 1 interferon production. Thus, IRF8 differentially controls the survival and function of terminally differentiated monocytes, cDC1s, and pDCs. ",

keywords = "IRF4, IRF8, dendritic cell, development, lineage, monocyte, plasmacytoid dendritic cell, terminal selector, transcription factor",

author = "Dorine Sichien and Scott, {Charlotte L} and Liesbet Martens and Matthias Vanderkerken and {Van Gassen}, Sofie and Maud Plantinga and Thorsten Joeris and {De Prijck}, Sofie and Leen Vanhoutte and Manon Vanheerswynghels and {Van Isterdael}, Gert and Wendy Toussaint and Madeira, {Filipe Branco} and Karl Vergote and Agace, {William Winston} and Clausen, {Bj{\"o}rn E.} and Hamida Hammad and Marc Dalod and Yvan Saeys and Lambrecht, {Bart N.} and Martin Guilliams",

year = "2016",

doi = "10.1016/j.immuni.2016.08.013",

language = "English",

volume = "45",

pages = "626--640",

journal = "Immunity",

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Sichien, D, Scott, CL, Martens, L, Vanderkerken, M, Van Gassen, S, Plantinga, M, Joeris, T, De Prijck, S, Vanhoutte, L, Vanheerswynghels, M, Van Isterdael, G, Toussaint, W, Madeira, FB, Vergote, K, Agace, WW, Clausen, BE, Hammad, H, Dalod, M, Saeys, Y, Lambrecht, BN & Guilliams, M 2016, 'IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively', Immunity, vol. 45, no. 3, pp. 626-640. https://doi.org/10.1016/j.immuni.2016.08.013

TY - JOUR

T1 - IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

AU - Sichien, Dorine

AU - Scott, Charlotte L

AU - Martens, Liesbet

AU - Vanderkerken, Matthias

AU - Van Gassen, Sofie

AU - Plantinga, Maud

AU - Joeris, Thorsten

AU - De Prijck, Sofie

AU - Vanhoutte, Leen

AU - Vanheerswynghels, Manon

AU - Van Isterdael, Gert

AU - Toussaint, Wendy

AU - Madeira, Filipe Branco

AU - Vergote, Karl

AU - Agace, William Winston

AU - Clausen, Björn E.

AU - Hammad, Hamida

AU - Dalod, Marc

AU - Saeys, Yvan

AU - Lambrecht, Bart N.

AU - Guilliams, Martin

PY - 2016

Y1 - 2016

N2 - Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the identity of terminally differentiated cells are designated "terminal selectors." Using BM chimeras, conditional Irf8(fl/fl) mice and various promotors to target Cre recombinase to different stages of monocyte and DC development, we have identified IRF8 as a terminal selector of the cDC1 lineage controlling survival. In monocytes, IRF8 was necessary during early but not late development. Complete or late deletion of IRF8 had no effect on pDC development or survival but altered their phenotype and gene-expression profile leading to increased T cell stimulatory function but decreased type 1 interferon production. Thus, IRF8 differentially controls the survival and function of terminally differentiated monocytes, cDC1s, and pDCs.

AB - Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the identity of terminally differentiated cells are designated "terminal selectors." Using BM chimeras, conditional Irf8(fl/fl) mice and various promotors to target Cre recombinase to different stages of monocyte and DC development, we have identified IRF8 as a terminal selector of the cDC1 lineage controlling survival. In monocytes, IRF8 was necessary during early but not late development. Complete or late deletion of IRF8 had no effect on pDC development or survival but altered their phenotype and gene-expression profile leading to increased T cell stimulatory function but decreased type 1 interferon production. Thus, IRF8 differentially controls the survival and function of terminally differentiated monocytes, cDC1s, and pDCs.

KW - IRF4

KW - IRF8

KW - dendritic cell

KW - development

KW - lineage

KW - monocyte

KW - plasmacytoid dendritic cell

KW - terminal selector

KW - transcription factor

U2 - 10.1016/j.immuni.2016.08.013

DO - 10.1016/j.immuni.2016.08.013

M3 - Journal article

C2 - 27637148

SN - 1074-7613

VL - 45

SP - 626

EP - 640

JO - Immunity

JF - Immunity

IS - 3

ER -

IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

Abstract

Keywords

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