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© Institut Pasteur - Photo by Perrine Bomme, Lise Chauveau & Olivier Schwartz, colorized by Jean-Marc Panaud
Cellule dendritique vue en microscopie électronique à balayage. Les cellules dendritiques sont cellules importantes de l'immunité. Elles sont indispensables à la mise en place de défenses contre les agents infectieux, les tumeurs ou les maladies auto-immunes. Elles interviennent également dans les processus de tolérance de greffes.
Publication : Nature communications

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

Team: Dendritic cells and adaptive immunity
Member: Pierre Guermonprez
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 28 Apr 2020

Anselmi G, Vaivode K, Dutertre CA, Bourdely P, Missolo-Koussou Y, Newell E, Hickman O, Wood K, Saxena A, Helft J, Ginhoux F, Guermonprez P

Link to Pubmed [PMID] – 32345968

Link to DOI – 10.1038/s41467-020-15937-y

Nat Commun 2020 Apr; 11(1): 2054

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.