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 & 1 others Martin Guilliams

    Research output: Contribution to journalJournal articleResearchpeer-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 languageEnglish
    JournalImmunity
    Volume45
    Issue number3
    Pages (from-to)626-640
    Number of pages15
    ISSN1074-7613
    DOIs
    Publication statusPublished - 2016

    Keywords

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

    Cite this

    Sichien, D., Scott, C. L., Martens, L., Vanderkerken, M., Van Gassen, S., Plantinga, M., ... 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
    Sichien, Dorine ; Scott, Charlotte L ; Martens, Liesbet ; Vanderkerken, Matthias ; Van Gassen, Sofie ; Plantinga, Maud ; Joeris, Thorsten ; De Prijck, Sofie ; Vanhoutte, Leen ; Vanheerswynghels, Manon ; Van Isterdael, Gert ; Toussaint, Wendy ; Madeira, Filipe Branco ; Vergote, Karl ; Agace, William Winston ; Clausen, Björn E. ; Hammad, Hamida ; Dalod, Marc ; Saeys, Yvan ; Lambrecht, Bart N. ; Guilliams, Martin. / IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively. In: Immunity. 2016 ; Vol. 45, No. 3. pp. 626-640.
    @article{4090ebba89bb4de69c70d6cf18bd2c0b,
    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

    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; Vanheerswynghels, Manon; Van Isterdael, Gert; Toussaint, Wendy; Madeira, Filipe Branco; Vergote, Karl; Agace, William Winston; Clausen, Björn E.; Hammad, Hamida; Dalod, Marc; Saeys, Yvan; Lambrecht, Bart N.; Guilliams, Martin.

    In: Immunity, Vol. 45, No. 3, 2016, p. 626-640.

    Research output: Contribution to journalJournal articleResearchpeer-review

    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

    VL - 45

    SP - 626

    EP - 640

    JO - Immunity

    JF - Immunity

    SN - 1074-7613

    IS - 3

    ER -