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

Sichien, Dorine; Scott, Charlotte L.; Martens, Liesbet; Vanderkerken, Matthias; Van Gassen, Sofie; Plantinga, Maud; Joeris, Thorsten; De Prijck, Sofie; Vanhoutte, Leen and Vanheerswynghels, Manon, et al. (2016) In Immunity 45(3). p.626-640
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 Irf8fl/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... (More)

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 Irf8fl/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.

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@article{31fecae9-1772-4d59-8221-aba1bcc21486,
  abstract     = {<p>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<sup>fl/fl</sup> 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.</p>},
  author       = {Sichien, Dorine and Scott, Charlotte L. and Martens, Liesbet and Vanderkerken, Matthias and Van Gassen, Sofie and Plantinga, Maud and Joeris, Thorsten and De Prijck, Sofie and Vanhoutte, Leen and Vanheerswynghels, Manon and Van Isterdael, Gert and Toussaint, Wendy and Madeira, Filipe Branco and Vergote, Karl and Agace, William W. and Clausen, Björn E. and Hammad, Hamida and Dalod, Marc and Saeys, Yvan and Lambrecht, Bart N. and Guilliams, Martin},
  issn         = {1074-7613},
  keyword      = {dendritic cell,development,IRF4,IRF8,lineage,monocyte,plasmacytoid dendritic cell,terminal selector,transcription factor},
  language     = {eng},
  month        = {09},
  number       = {3},
  pages        = {626--640},
  publisher    = {Cell Press},
  series       = {Immunity},
  title        = {IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively},
  url          = {http://dx.doi.org/10.1016/j.immuni.2016.08.013},
  volume       = {45},
  year         = {2016},
}