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Ikaros family zinc finger 1 regulates dendritic cell development and function in humans

Author

Listed:
  • Urszula Cytlak

    (Newcastle University)

  • Anastasia Resteu

    (Newcastle University)

  • Delfien Bogaert

    (Ghent University Hospital
    Ghent University Hospital
    Ghent University Hospital
    Ghent University Hospital)

  • Hye Sun Kuehn

    (National Institutes of Health)

  • Thomas Altmann

    (Newcastle University
    Newcastle upon Tyne Hospitals NHS Foundation Trust)

  • Andrew Gennery

    (Newcastle University
    Newcastle upon Tyne Hospitals NHS Foundation Trust)

  • Graham Jackson

    (Newcastle upon Tyne Hospitals NHS Foundation Trust
    Newcastle University)

  • Attila Kumanovics

    (University of Utah)

  • Karl V. Voelkerding

    (University of Utah)

  • Seraina Prader

    (University Children’s Hospital Zurich)

  • Melissa Dullaers

    (Ghent University Hospital
    Ghent University Hospital
    Ghent University)

  • Janine Reichenbach

    (University Children’s Hospital Zurich
    University Children’s Hospital Zurich
    University of Zurich
    University of Zurich)

  • Harry Hill

    (University of Utah
    University of Utah)

  • Filomeen Haerynck

    (Ghent University Hospital
    Ghent University Hospital
    Ghent University Hospital)

  • Sergio D. Rosenzweig

    (National Institutes of Health)

  • Matthew Collin

    (Newcastle University
    Newcastle upon Tyne Hospitals NHS Foundation Trust)

  • Venetia Bigley

    (Newcastle University
    Newcastle upon Tyne Hospitals NHS Foundation Trust)

Abstract

Ikaros family zinc finger 1 (IKZF1) is a haematopoietic transcription factor required for mammalian B-cell development. IKZF1 deficiency also reduces plasmacytoid dendritic cell (pDC) numbers in mice, but its effects on human DC development are unknown. Here we show that heterozygous mutation of IKZF1 in human decreases pDC numbers and expands conventional DC1 (cDC1). Lenalidomide, a drug that induces proteosomal degradation of IKZF1, also decreases pDC numbers in vivo, and reduces the ratio of pDC/cDC1 differentiated from progenitor cells in vitro in a dose-dependent manner. In addition, non-classical monocytes are reduced by IKZF1 deficiency in vivo. DC and monocytes from patients with IKZF1 deficiency or lenalidomide-treated cultures secrete less IFN-α, TNF and IL-12. These results indicate that human DC development and function are regulated by IKZF1, providing further insights into the consequences of IKZF1 mutation on immune function and the mechanism of immunomodulation by lenalidomide.

Suggested Citation

  • Urszula Cytlak & Anastasia Resteu & Delfien Bogaert & Hye Sun Kuehn & Thomas Altmann & Andrew Gennery & Graham Jackson & Attila Kumanovics & Karl V. Voelkerding & Seraina Prader & Melissa Dullaers & J, 2018. "Ikaros family zinc finger 1 regulates dendritic cell development and function in humans," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02977-8
    DOI: 10.1038/s41467-018-02977-8
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    Cited by:

    1. Qiang Wang & Taehyeung Kim & Marta Martínez-Bonet & Vitor R. C. Aguiar & Sangwan Sim & Jing Cui & Jeffrey A. Sparks & Xiaoting Chen & Marc Todd & Brian Wauford & Miranda C. Marion & Carl D. Langefeld , 2024. "High-throughput identification of functional regulatory SNPs in systemic lupus erythematosus," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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