Engineered niches support the development of human dendritic cells in humanized mice.
Animals
Biomarkers
/ metabolism
Bone Marrow Cells
/ cytology
Cell Differentiation
/ drug effects
Cell Membrane
/ drug effects
Chemokine CXCL12
/ pharmacology
Cluster Analysis
Collagen
/ pharmacology
Dendritic Cells
/ cytology
Drug Combinations
Humans
Laminin
/ pharmacology
Membrane Proteins
/ metabolism
Mice
Organoids
/ drug effects
Proteoglycans
/ pharmacology
Stem Cell Niche
/ drug effects
Stromal Cells
/ cytology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 04 2020
28 04 2020
Historique:
received:
25
10
2018
accepted:
18
03
2020
entrez:
30
4
2020
pubmed:
30
4
2020
medline:
30
7
2020
Statut:
epublish
Résumé
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
Identifiants
pubmed: 32345968
doi: 10.1038/s41467-020-15937-y
pii: 10.1038/s41467-020-15937-y
pmc: PMC7189247
doi:
Substances chimiques
Biomarkers
0
Chemokine CXCL12
0
Drug Combinations
0
Laminin
0
Membrane Proteins
0
Proteoglycans
0
flt3 ligand protein
0
matrigel
119978-18-6
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2054Subventions
Organisme : Cancer Research UK (CRUK)
ID : C57672/A22369
Pays : International
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M029735/1
Pays : United Kingdom
Références
Banchereau, J. & Steinman, R. M. Dendritic cells and the control of immunity. Nature 392, 245–252 (1998).
pubmed: 9521319
doi: 10.1038/32588
pmcid: 9521319
Steinman, R. M., Hawiger, D. & Nussenzweig, M. C. Tolerogenic dendritic cells. Annu Rev. Immunol. 21, 685–711 (2003).
pubmed: 12615891
doi: 10.1146/annurev.immunol.21.120601.141040
pmcid: 12615891
Palucka, K. & Banchereau, J. Dendritic-cell-based therapeutic cancer vaccines. Immunity 39, 38–48 (2013).
pubmed: 23890062
pmcid: 3788678
doi: 10.1016/j.immuni.2013.07.004
Bachem, A. et al. Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J. Exp. Med. 207, 1273–1281 (2010).
pubmed: 20479115
pmcid: 2882837
doi: 10.1084/jem.20100348
Crozat, K. et al. The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells. J. Exp. Med. 207, 1283–1292 (2010).
pubmed: 20479118
pmcid: 2882835
doi: 10.1084/jem.20100223
Jongbloed, S. L. et al. Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J. Exp. Med. 207, 1247–1260 (2010).
pubmed: 20479116
pmcid: 2882828
doi: 10.1084/jem.20092140
Lee, J. et al. Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow. J. Exp. Med. 212, 385–399 (2015).
pubmed: 25687283
pmcid: 4354373
doi: 10.1084/jem.20141442
Helft, J. et al. Dendritic cell lineage potential in human early hematopoietic progenitors. Cell Rep. 20, 529–537 (2017).
pubmed: 28723558
pmcid: 5529209
doi: 10.1016/j.celrep.2017.06.075
Lee, J. et al. Lineage specification of human dendritic cells is marked by IRF8 expression in hematopoietic stem cells and multipotent progenitors. Nat. Immunol. 18, 877–888 (2017).
pubmed: 28650480
pmcid: 5743223
doi: 10.1038/ni.3789
Breton, G. et al. Circulating precursors of human CD1c+ and CD141+ dendritic cells. J. Exp. Med. 212, 401–413 (2015).
pubmed: 25687281
pmcid: 4354370
doi: 10.1084/jem.20141441
Breton, G. et al. Human dendritic cells (DCs) are derived from distinct circulating precursors that are precommitted to become CD1c+ or CD141+ DCs. J. Exp. Med. 213, 2861–2870 (2016).
pubmed: 27864467
pmcid: 5154947
doi: 10.1084/jem.20161135
See, P. et al. Mapping the human DC lineage through the integration of high-dimensional techniques. Science 356, pii: eaag3009 (2017).
Poulin, L. F. et al. DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and nonlymphoid tissues. Blood 119, 6052–6062 (2012).
pubmed: 22442345
doi: 10.1182/blood-2012-01-406967
pmcid: 22442345
Montoya, M. et al. Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 99, 3263–3271 (2002).
pubmed: 11964292
doi: 10.1182/blood.V99.9.3263
pmcid: 11964292
Haniffa, M. et al. Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity 37, 60–73 (2012).
pubmed: 22795876
pmcid: 3476529
doi: 10.1016/j.immuni.2012.04.012
Schlitzer, A. et al. IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL
pubmed: 23706669
pmcid: 3666057
doi: 10.1016/j.immuni.2013.04.011
Tamura, T. et al. IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity. J. Immunol. 174, 2573–2581 (2005).
pubmed: 15728463
doi: 10.4049/jimmunol.174.5.2573
pmcid: 15728463
Segura, E. et al. Human inflammatory dendritic cells induce Th17 cell differentiation. Immunity 38, 336–348 (2013).
pubmed: 23352235
doi: 10.1016/j.immuni.2012.10.018
pmcid: 23352235
Segura, E. et al. Characterization of resident and migratory dendritic cells in human lymph nodes. J. Exp. Med. 209, 653–660 (2012).
pubmed: 22430490
pmcid: 3328358
doi: 10.1084/jem.20111457
Villani, A. C. et al. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science 356, pii: eaah4573(2017).
Barker, J. E. Sl/Sld hematopoietic progenitors are deficient in situ. Exp. Hematol. 22, 174–177 (1994).
pubmed: 7507859
pmcid: 7507859
Barker, J. E. Early transplantation to a normal microenvironment prevents the development of Steel hematopoietic stem cell defects. Exp. Hematol. 25, 542–547 (1997).
pubmed: 9197334
pmcid: 9197334
Greenbaum, A. et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 495, 227–230 (2013).
pubmed: 23434756
pmcid: 3600148
doi: 10.1038/nature11926
Dar, A. et al. Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nat. Immunol. 6, 1038–1046 (2005).
pubmed: 16170318
doi: 10.1038/ni1251
pmcid: 16170318
Qian, H. et al. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell 1, 671–684 (2007).
pubmed: 18371408
doi: 10.1016/j.stem.2007.10.008
pmcid: 18371408
Yoshihara, H. et al. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell 1, 685–697 (2007).
pubmed: 18371409
doi: 10.1016/j.stem.2007.10.020
pmcid: 18371409
Mendelson, A. & Frenette, P. S. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat. Med. 20, 833–846 (2014).
pubmed: 25100529
pmcid: 4459580
doi: 10.1038/nm.3647
Guermonprez, P. et al. Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection. Nat. Med. 19, 730–738 (2013).
pubmed: 23685841
pmcid: 3914008
doi: 10.1038/nm.3197
Saito, Y., Boddupalli, C. S., Borsotti, C. & Manz, M. G. Dendritic cell homeostasis is maintained by nonhematopoietic and T-cell-produced Flt3-ligand in steady state and during immune responses. Eur. J. Immunol. 43, 1651–1658 (2013).
pubmed: 23519969
doi: 10.1002/eji.201243163
pmcid: 23519969
Eidenschenk, C. et al. Flt3 permits survival during infection by rendering dendritic cells competent to activate NK cells. Proc. Natl Acad. Sci. USA 107, 9759–9764 (2010).
pubmed: 20457904
doi: 10.1073/pnas.1005186107
pmcid: 20457904
Ginhoux, F. et al. The origin and development of nonlymphoid tissue CD103+ DCs. J. Exp. Med. 206, 3115–3130 (2009).
pubmed: 20008528
pmcid: 2806447
doi: 10.1084/jem.20091756
Malhotra, D. et al. Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks. Nat. Immunol. 13, 499–510 (2012).
pubmed: 22466668
pmcid: 3366863
doi: 10.1038/ni.2262
Waskow, C. et al. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat. Immunol. 9, 676–683 (2008).
pubmed: 18469816
pmcid: 2746085
doi: 10.1038/ni.1615
Liu, K. et al. Origin of dendritic cells in peripheral lymphoid organs of mice. Nat. Immunol. 8, 578–583 (2007).
pubmed: 17450143
doi: 10.1038/ni1462
pmcid: 17450143
Caux, C., Dezutter-Dambuyant, C., Schmitt, D. & Banchereau, J. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360, 258–261 (1992).
pubmed: 1279441
doi: 10.1038/360258a0
pmcid: 1279441
Sallusto, F. & Lanzavecchia, A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J. Exp. Med. 179, 1109–1118 (1994).
pubmed: 8145033
doi: 10.1084/jem.179.4.1109
pmcid: 8145033
Proietto, A. I., Mittag, D., Roberts, A. W., Sprigg, N. & Wu, L. The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34(+) stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin. Cell. Mol. Immunol. 9, 446–454 (2012).
pubmed: 23085949
pmcid: 4002222
doi: 10.1038/cmi.2012.48
Balan, S. et al. Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells. J. Immunol. 193, 1622–1635 (2014).
pubmed: 25009205
pmcid: 4120898
doi: 10.4049/jimmunol.1401243
Poulin, L. F. et al. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells. J. Exp. Med. 207, 1261–1271 (2010).
pubmed: 20479117
pmcid: 2882845
doi: 10.1084/jem.20092618
Lyman, S. D. et al. Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells. Cell 75, 1157–1167 (1993).
pubmed: 7505204
doi: 10.1016/0092-8674(93)90325-K
pmcid: 7505204
Rosnet, O. et al. Human FLT3/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells. Leukemia 10, 238–248 (1996).
pubmed: 8637232
pmcid: 8637232
McKenna, H. J. et al. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 95, 3489–3497 (2000).
pubmed: 10828034
doi: 10.1182/blood.V95.11.3489
pmcid: 10828034
Maraskovsky, E. et al. Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified. J. Exp. Med. 184, 1953–1962 (1996).
pubmed: 8920882
doi: 10.1084/jem.184.5.1953
pmcid: 8920882
Pulendran, B. et al. Flt3-ligand and granulocyte colony-stimulating factor mobilize distinct human dendritic cell subsets in vivo. J. Immunol. 165, 566–572 (2000).
pubmed: 10861097
doi: 10.4049/jimmunol.165.1.566
pmcid: 10861097
Onai, N., Obata-Onai, A., Tussiwand, R., Lanzavecchia, A. & Manz, M. G. Activation of the Flt3 signal transduction cascade rescues and enhances type I interferon-producing and dendritic cell development. J. Exp. Med. 203, 227–238 (2006).
pubmed: 16418395
pmcid: 2118073
doi: 10.1084/jem.20051645
Kirkling, M. E. et al. Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells. Cell Rep. 23, 3658–3672 e3656 (2018).
pubmed: 29925006
pmcid: 6063084
doi: 10.1016/j.celrep.2018.05.068
Balan, S. et al. Large-scale human dendritic cell differentiation revealing Notch-dependent lineage bifurcation and heterogeneity. Cell Rep. 24, 1902–1915 e1906 (2018).
pubmed: 30110645
pmcid: 6113934
doi: 10.1016/j.celrep.2018.07.033
Ding, Y. et al. FLT3-ligand treatment of humanized mice results in the generation of large numbers of CD141+ and CD1c+ dendritic cells in vivo. J. Immunol. 192, 1982–1989 (2014).
pubmed: 24453245
doi: 10.4049/jimmunol.1302391
pmcid: 24453245
Li, Y. et al. A novel Flt3-deficient HIS mouse model with selective enhancement of human DC development. Eur. J. Immunol. 46, 1291–1299 (2016).
pubmed: 26865269
doi: 10.1002/eji.201546132
pmcid: 26865269
Yu, C. I. et al. Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal effector T cells via the cytokine TGF-beta. Immunity 38, 818–830 (2013).
pubmed: 23562160
pmcid: 3639491
doi: 10.1016/j.immuni.2013.03.004
Itoh, K. et al. Reproducible establishment of hemopoietic supportive stromal cell lines from murine bone marrow. Exp. Hematol. 17, 145–153 (1989).
pubmed: 2783573
pmcid: 2783573
Nakano, T., Kodama, H. & Honjo, T. Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science 265, 1098–1101 (1994).
pubmed: 8066449
doi: 10.1126/science.8066449
pmcid: 8066449
Ding, L., Saunders, T. L., Enikolopov, G. & Morrison, S. J. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481, 457–462 (2012).
pubmed: 22281595
pmcid: 22281595
doi: 10.1038/nature10783
Caux, C. et al. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha. J. Exp. Med. 184, 695–706 (1996).
pubmed: 8760823
doi: 10.1084/jem.184.2.695
pmcid: 8760823
Alcantara-Hernandez, M. et al. High-dimensional phenotypic mapping of human dendritic cells reveals interindividual variation and tissue specialization. Immunity 47, 1037–1050 e1036 (2017).
pubmed: 29221729
pmcid: 5738280
doi: 10.1016/j.immuni.2017.11.001
Xu, Y., Zhan, Y., Lew, A. M., Naik, S. H. & Kershaw, M. H. Differential development of murine dendritic cells by GM-CSF versus Flt3 ligand has implications for inflammation and trafficking. J. Immunol. 179, 7577–7584 (2007).
pubmed: 18025203
doi: 10.4049/jimmunol.179.11.7577
pmcid: 18025203
Naik, S. H. et al. Cutting edge: generation of splenic CD8+ and CD8- dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures. J. Immunol. 174, 6592–6597 (2005).
pubmed: 15905497
doi: 10.4049/jimmunol.174.11.6592
pmcid: 15905497
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
doi: 10.1073/pnas.0506580102
Spinelli, L., Carpentier, S., Montanana Sanchis, F., Dalod, M. & Vu Manh, T. P. BubbleGUM: automatic extraction of phenotype molecular signatures and comprehensive visualization of multiple Gene Set Enrichment Analyses. BMC Genomics 16, 814 (2015).
pubmed: 26481321
pmcid: 4617899
doi: 10.1186/s12864-015-2012-4
McGovern, N. et al. Human dermal CD14(+) cells are a transient population of monocyte-derived macrophages. Immunity 41, 465–477 (2014).
pubmed: 25200712
pmcid: 4175180
doi: 10.1016/j.immuni.2014.08.006
Becht, E. et al. Evaluation of UMAP as an alternative to t-SNE for single-cell data. bioRxiv https://doi.org/10.1101/298430 (2018).
Yin, X. et al. Human blood CD1c+ dendritic cells encompass CD5high and CD5low subsets that differ significantly in phenotype, gene expression, and functions. J. Immunol. 198, 1553–1564 (2017).
pubmed: 28087664
doi: 10.4049/jimmunol.1600193
pmcid: 28087664
Dutertre, C. A. et al. Single-cell analysis of human mononuclear phagocytes reveals subset-defining markers and identifies circulating inflammatory dendritic cells. Immunity 51, 573–589 e578 (2019).
pubmed: 31474513
doi: 10.1016/j.immuni.2019.08.008
pmcid: 31474513
Bonifaz, L. et al. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J. Exp. Med. 196, 1627–1638 (2002).
pubmed: 12486105
pmcid: 2196060
doi: 10.1084/jem.20021598
Toksoz, D. et al. Support of human hematopoiesis in long-term bone marrow cultures by murine stromal cells selectively expressing the membrane-bound and secreted forms of the human homolog of the steel gene product, stem cell factor. Proc. Natl Acad. Sci. USA 89, 7350–7354 (1992).
pubmed: 1380155
doi: 10.1073/pnas.89.16.7350
pmcid: 1380155
Takagi, S. et al. Membrane-bound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation. Blood 119, 2768–2777 (2012).
pubmed: 22279057
pmcid: 3327455
doi: 10.1182/blood-2011-05-353201
Kong, X. F. et al. Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency. Nat. Immunol. 19, 973–985 (2018).
pubmed: 30127434
pmcid: 6130844
doi: 10.1038/s41590-018-0178-z
Rongvaux, A. et al. Development and function of human innate immune cells in a humanized mouse model. Nat. Biotechnol. 32, 364–372 (2014).
pubmed: 24633240
pmcid: 4017589
doi: 10.1038/nbt.2858
Nicolini, F. E., Cashman, J. D., Hogge, D. E., Humphries, R. K. & Eaves, C. J. NOD/SCID mice engineered to express human IL
pubmed: 14628073
doi: 10.1038/sj.leu.2403222
pmcid: 14628073
Ito, R. et al. Establishment of a human allergy model using human IL-3/GM-CSF-transgenic NOG mice. J. Immunol. 191, 2890–2899 (2013).
pubmed: 23956433
doi: 10.4049/jimmunol.1203543
pmcid: 23956433
Willinger, T. et al. Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung. Proc. Natl Acad. Sci. USA 108, 2390–2395 (2011).
pubmed: 21262803
doi: 10.1073/pnas.1019682108
pmcid: 21262803
Orimo, A. et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121, 335–348 (2005).
doi: 10.1016/j.cell.2005.02.034
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
pubmed: 23104886
doi: 10.1093/bioinformatics/bts635
pmcid: 23104886
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8
Benjamini, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B Methodol. 57, 289–300 (1995).
Wickham, H. ggplot2: elegant graphics for data analysis (Springer Science & Business Media, 2009).
Kamburov, A., Wierling, C., Lehrach, H. & Herwig, R. ConsensusPathDB-a database for integrating human functional interaction networks. Nucleic Acids Res. 37, D623–628 (2009).
pubmed: 18940869
doi: 10.1093/nar/gkn698
pmcid: 18940869
Becher, B. et al. High-dimensional analysis of the murine myeloid cell system. Nat. Immunol. 15, 1181–1189 (2014).
pubmed: 25306126
doi: 10.1038/ni.3006
pmcid: 25306126
Finck, R. et al. Normalization of mass cytometry data with bead standards. Cytom. A 83, 483–494 (2013).
doi: 10.1002/cyto.a.22271
Newell, E. W., Sigal, N., Bendall, S. C., Nolan, G. P. & Davis, M. M. Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity 36, 142–152 (2012).
pubmed: 22265676
pmcid: 3752833
doi: 10.1016/j.immuni.2012.01.002
Parks, D. R., Roederer, M. & Moore, W. A. A new “Logicle” display method avoids deceptive effects of logarithmic scaling for low signals and compensated data. Cytom. A 69, 541–551 (2006).
doi: 10.1002/cyto.a.20258
McInnes, L. & Healy, J. UMAP: uniform manifold approximation and projection for dimension reduction. Preprint at arXiv:1802.03426 (2018).