Engineered niches support the development of human dendritic cells in humanized mice.
Giorgio AnselmiKristine VaivodeCharles-Antoine DutertrePierre BourdelyYoann Missolo-KoussouEvan NewellOliver HickmanKristie WoodAlka SaxenaJulie HelftFlorent GinhouxPierre GuermonprezPublished in: Nature communications (2020)
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.
Keyphrases
- dendritic cells
- endothelial cells
- stem cells
- bone marrow
- induced pluripotent stem cells
- immune response
- cell cycle
- pluripotent stem cells
- tyrosine kinase
- acute myeloid leukemia
- induced apoptosis
- type diabetes
- metabolic syndrome
- regulatory t cells
- cell proliferation
- mesenchymal stem cells
- high fat diet induced
- cell death
- insulin resistance
- skeletal muscle
- endoplasmic reticulum stress