Year: 2020
Type: article
Abstract: Classical dendritic cells (cDCs) are rare sentinel cells specialized in the regulation of adaptive immunity. Modeling cDC development is both crucial to study cDCs and harness their potential in immunotherapy. Here we addressed whether cDCs could differentiate in response to trophic cues delivered by mesenchymal components of the hematopoietic niche where they physiologically develop and maintain. We found that expression of the membrane bound form of human FLT3L and SCF together with CXCL12 in a bone marrow mesenchymal stromal cell line is sufficient to induce the contact-dependent specification of both type 1 and type 2 cDCs from CD34 + hematopoietic stem and progenitor cells (HSPCs). Engraftment of these engineered mesenchymal stromal cells (eMSCs) together with CD34 + HSPCs creates an in vivo synthetic niche in the dermis of immunodeficient mice. Cell-to-cell contact between HSPCs and stromal cells within these organoids drive the local specification of cDCs and CD123 + AXL + CD327 + pre/AS-DCs. cDCs generated in vivo display higher levels of resemblance with human blood cDCs unattained by in vitro generated subsets. Altogether, eMSCs provide a novel and unique platform recapitulating the full spectrum of cDC subsets enabling their functional characterization in vivo .
Source: Nature Communications
Institutions: King's College London, Cancer Research UK, University of Oxford, MRC Weatherall Institute of Molecular Medicine, Kings Health Partners, Agency for Science, Technology and Research, Singapore Immunology Network, Inserm, Université Paris Sciences et Lettres, Institut Curie, Institute of Cancer Research, St Thomas' Hospital, Centre National de la Recherche Scientifique, Université Paris Cité, Centre de Recherche sur l'Inflammation
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Funders: Anthony Nolan, Cancer Research UK, National Institute for Health and Care Research, King's College London, National Centre for the Replacement, Refinement and Reduction of Animals in Research, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, King's Health Partners, Centre National de la Recherche Scientifique, Institut National Du Cancer, Direction Générale de l’offre de Soins, Institut Curie, National Centre for the Replacement Refinement and Reduction of Animals in Research, Biotechnology and Biological Sciences Research Council
Awards: G1435997383, G1608086581, G2045273392, Paris Sciences et Lettres, G3231222199, Antigen presentation by MHCII in cross-presenting dendritic cells., G4190806336, G4656594441, G471331628, Dynamics of Dendritic Cell populations during inflammation, Biologie des cellules dendritiques, G5610283560, Development and function of inflammatory dendritic cells, G6759105742, G6803667113, G683439542, G7240651115, G7317887839, G782245399, G8471630636, G8495868730, Université de Paris, G853837045, G937427620
OpenAlex ID: W3018586675