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Engineered niches support the development of human dendritic cells in humanized mice

Author

Listed:
  • Giorgio Anselmi

    (King’s College London
    King’s College London
    University of Oxford)

  • Kristine Vaivode

    (King’s College London
    King’s College London)

  • Charles-Antoine Dutertre

    (A*STAR)

  • Pierre Bourdely

    (King’s College London
    King’s College London)

  • Yoann Missolo-Koussou

    (INSERM U932 & SiRIC, Translational Immunotherapy Team)

  • Evan Newell

    (A*STAR)

  • Oliver Hickman

    (King’s College London
    King’s College London
    Institute of Cancer Research)

  • Kristie Wood

    (National Institute of Health Research Biomedical Research Centre at Guy’s and St Thomas’ Hospital and King’s College London
    Labcyte Ltd)

  • Alka Saxena

    (National Institute of Health Research Biomedical Research Centre at Guy’s and St Thomas’ Hospital and King’s College London)

  • Julie Helft

    (INSERM U932 & SiRIC, Translational Immunotherapy Team)

  • Florent Ginhoux

    (A*STAR)

  • Pierre Guermonprez

    (King’s College London
    King’s College London
    Université de Paris, Centre for Inflammation Research, CNRS ERL8252, INSERM1149)

Abstract

Classical dendritic cells (cDCs) are rare sentinel cells specialized in the regulation of adaptive immunity. Modeling cDC development is crucial to study cDCs and harness their therapeutic potential. Here we address whether cDCs could differentiate in response to trophic cues delivered by mesenchymal components of the hematopoietic niche. We find that mesenchymal stromal cells engineered to express membrane-bound FLT3L and stem cell factor (SCF) together with CXCL12 induce the specification of human cDCs from CD34+ hematopoietic stem and progenitor cells (HSPCs). Engraftment of engineered mesenchymal stromal cells (eMSCs) together with CD34+ HSPCs creates an in vivo synthetic niche in the dermis of immunodeficient mice driving the differentiation of cDCs and CD123+AXL+CD327+ pre/AS-DCs. cDC2s generated in vivo display higher levels of resemblance with human blood cDCs unattained by in vitro-generated subsets. Altogether, eMSCs provide a unique platform recapitulating the full spectrum of cDC subsets enabling their functional characterization in vivo.

Suggested Citation

  • Giorgio Anselmi & Kristine Vaivode & Charles-Antoine Dutertre & Pierre Bourdely & Yoann Missolo-Koussou & Evan Newell & Oliver Hickman & Kristie Wood & Alka Saxena & Julie Helft & Florent Ginhoux & Pi, 2020. "Engineered niches support the development of human dendritic cells in humanized mice," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15937-y
    DOI: 10.1038/s41467-020-15937-y
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