CoChat
Sign Up
Cited by 386Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyHematopoietic Stem Cell Transplantation

The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3

Open access
D'Amico, Angela, Wu, Li·2003·The Journal of Experimental Medicine
DOI 10.1084/jem.20030107PMC PMC2194069
Open this paper in CoChat — free accountOpen PDF

Abstract

Flt3 ligand (Flt3L) is a growth factor for hemopoietic progenitors and can promote the expansion of both conventional dendritic cells (DCs) and plasmacytoid predendritic cells (p-preDCs). The cells responding to Flt3L treatment and the precursors for the DCs and p-preDCs had not been fully characterized. We examined different mouse bone marrow (BM) hemopoietic precursor populations for the surface expression of Flt3 and tested them for early DC and p-preDC precursor activity. Most DC precursor activity, other than that given by multipotent hemopoietic stem cells, was within the downstream precursors expressing Flt3. The majority of mouse BM common lymphoid precursors expressed high levels of Flt3 and these were the most efficient precursors of both DCs and p-preDCs. In contrast, only a small proportion of the common myeloid precursors (CMPs) expressed Flt3, but the precursor activity for both DCs and p-preDCs was within this minor Flt3+ CMP fraction. The granulocyte and macrophage precursors and pro-B cells did not express Flt3 and had no DC or p-preDC precursor activity. These findings demonstrate that the early precursors for all DC subtypes are within the BM Flt3+ precursor populations, regardless of their lymphoid or myeloid lineage orientation.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1084/jem.20030107

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 33

  1. [1]Lyman, S.D., L. James, T. Vanden Bos, P. de Vries, K. Brasel, B. Gliniak, L.T. Hollingsworth, K.S. Picha, H.J. McKenna, R.R. Splett, et al. 1993. Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells. Cell. 75: 1157–1167. 7505204
  2. [2]Hannum, C., J. Culpepper, D. Campbell, T. McClanahan, S. Zurawski, J.F. Bazan, R. Kastelein, S. Hudak, J. Wagner, J. Mattson, et al. 1994. Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs. Nature. 368: 643–648. 8145851
  3. [3]Gilliland, D.G., and J.D. Griffin. 2002. The roles of FLT3 in hematopoiesis and leukemia. Blood. 100: 1532–1542. 12176867
  4. [4]Rasko, J.E., D. Metcalf, M.T. Rossner, C.G. Begley, and N.A. Nicola. 1995. The flt3/flk-2 ligand: receptor distribution and action on murine haemopoietic cell survival and proliferation. Leukemia. 9: 2058–2066. 8609717
  5. [5]Brasel, K., S. Escobar, R. Anderberg, P. de Vries, H.J. Gruss, and S.D. Lyman. 1995. Expression of the flt3 receptor and its ligand on hematopoietic cells. Leukemia. 9: 1212–1218. 7630197
  6. [6]Turner, A.M., N.L. Lin, S. Issarachai, S.D. Lyman, and V.C. Broudy. 1996. FLT3 receptor expression on the surface of normal and malignant human hematopoietic cells. Blood. 88: 3383–3390. 8896403
  7. [7]Rosnet, O., H.J. Buhring, S. Marchetto, I. Rappold, C. Lavagna, D. Sainty, C. Arnoulet, C. Chabannon, L. Kanz, C. Hannum, et al. 1996. Human FLT3/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells. Leukemia. 10: 238–248. 8637232
  8. [8]Adolfsson, J., O.J. Borge, D. Bryder, K. Theilgaard-Monch, I. Astrand-Grundstrom, E. Sitnicka, Y. Sasaki, and S.E. Jacobsen. 2001. Upregulation of Flt3 expression within the bone marrow Lin(−)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity. 15: 659–669. 11672547
  9. [9]Christensen, J.L., and I.L. Weissman. 2001. Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc. Natl. Acad. Sci. USA. 98: 14541–14546. 11724967 PMC64718
  10. [10]Maraskovsky, E., K. Brasel, M. Teepe, E.R. Roux, S.D. Lyman, K. Shortman, and H.J. McKenna. 1996. 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. 8920882 PMC2192888
  11. [11]Drakes, M.L., L. Lu, V.M. Subbotin, and A.W. Thomson. 1997. In vivo administration of flt3 ligand markedly stimulates generation of dendritic cell progenitors from mouse liver. J. Immunol. 159: 4268–4278. 9379022
  12. [12]Lynch, D.H. 1998. Induction of dendritic cells (DC) by Flt3 Ligand (FL) promotes the generation of tumor-specific immune responses in vivo. Crit. Rev. Immunol. 18: 99–107. 9419452
  13. [13]Maraskovsky, E., E. Daro, E. Roux, M. Teepe, C.R. Maliszewski, J. Hoek, D. Caron, M.E. Lebsack, and H.J. McKenna. 2000. In vivo generation of human dendritic cell subsets by Flt3 ligand. Blood. 96: 878–884. 10910900
  14. [14]McKenna, H.J. 2001. Role of hematopoietic growth factors/flt3 ligand in expansion and regulation of dendritic cells. Curr. Opin. Hematol. 8: 149–154. 11303147
  15. [15]O'Keeffe, M., H. Hochrein, D. Vremec, J. Pooley, R. Evans, S. Woulfe, and K. Shortman. 2002. Effects of administration of progenipoietin 1, Flt-3 ligand, granulocyte colony-stimulating factor, and pegylated granulocyte-macrophage colony-stimulating factor on dendritic cell subsets in mice. Blood. 99: 2122–2130. 11877288
  16. [16]Bjorck, P. 2001. Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice. Blood. 98: 3520–3526. 11739152
  17. [17]McKenna, H.J., K.L. Stocking, R.E. Miller, K. Brasel, T. De Smedt, E. Maraskovsky, C.R. Maliszewski, D.H. Lynch, J. Smith, B. Pulendran, et al. 2000. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood. 95: 3489–3497. 10828034
  18. [18]Saunders, D., K. Lucas, J. Ismaili, L. Wu, E. Maraskovsky, A. Dunn, D. Metcalf, and K. Shortman. 1996. Dendritic cell development in culture from thymic precursor cells in the absence of granulocyte-macrophage colony-stimulating factor. J. Exp. Med. 184: 2185–2196. 8976174 PMC2196371
  19. [19]Brasel, K., T. De Smedt, J.L. Smith, and C.R. Maliszewski. 2000. Generation of murine dendritic cells from flt3-ligand-supplemented bone marrow cultures. Blood. 96: 3029–3039. 11049981
  20. [20]Gilliet, M., A. Boonstra, C. Paturel, S. Antonenko, X.L. Xu, G. Trinchieri, A. O'Garra, and Y.J. Liu. 2002. The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3 ligand and granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 195: 953–958. 11927638 PMC2193725
  21. [21]Brawand, P., D.R. Fitzpatrick, B.W. Greenfield, K. Brasel, C.R. Maliszewski, and T. De Smedt. 2002. Murine plasmacytoid pre-dendritic cells generated from flt3 ligand-supplemented bone marrow cultures are immature APCs. J. Immunol. 169: 6711–6719. 12471102
  22. [22]Bruno, L., T. Seidl, and A. Lanzavecchia. 2001. Mouse pre-immunocytes as non-proliferating multipotent precursors of macrophages, interferon-producing cells, CD8alpha(+) and CD8alpha(−) dendritic cells. Eur. J. Immunol. 31: 3403–3412. 11745359
  23. [23]Asselin-Paturel, C., A. Boonstra, M. Dalod, I. Durand, N. Yessaad, C. Dezutter-Dambuyant, A. Vicari, A. O'Garra, C. Biron, F. Briere, et al. 2001. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat. Immunol. 2: 1144–1150. 11713464
  24. [24]Nakano, H., M. Yanagita, and M.D. Gunn. 2001. CD11c(+)B220(+)Gr-1(+) cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells. J. Exp. Med. 194: 1171–1178. 11602645 PMC2193516
  25. [25]O'Keeffe, M., H. Hochrein, D. Vremec, B. Scott, P. Hertzog, L. Tatarczuch, and K. Shortman. 2002. Dendritic cell precursor populations of mouse blood: identification of the murine homologues of human blood plasmacytoid pre-DC2 and CD11c+ DC1 precursors. Blood. 101: 1453–1459. 12393665
  26. [26]O'Keeffe, M., H. Hochrein, D. Vremec, I. Caminschi, J.L. Miller, E.M. Anders, L. Wu, M.H. Lahoud, S. Henri, B. Scott, et al. 2002. Mouse plasmacytoid cells: long-lived cells, heterogeneous in surface phenotype and function, that differentiate into CD8+ dendritic cells only after microbial stimulus. J. Exp. Med. 196: 1307–1319. 12438422 PMC2193989
  27. [28]Wu, L., A. D'Amico, H. Hochrein, M. O'Keeffe, K. Shortman, and K. Lucas. 2001. Development of thymic and splenic dendritic cell populations from different hemopoietic precursors. Blood. 98: 3376–3382. 11719377
  28. [29]Kondo, M., I.L. Weissman, and K. Akashi. 1997. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell. 91: 661–672. 9393859
  29. [31]Manz, M.G., D. Traver, T. Miyamoto, I.L. Weissman, and K. Akashi. 2001. Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood. 97: 3333–3341. 11369621
  30. [32]Traver, D., K. Akashi, M. Manz, M. Merad, T. Miyamoto, E.G. Engleman, and I.L. Weissman. 2000. Development of CD8alpha-positive dendritic cells from a common myeloid progenitor. Science. 290: 2152–2154. 11118150
  31. [33]Corcoran, L., I. Ferrero, D. Vremec, M. O'Keeffe, L. Wu, A. Wilson, and K. Shortman. 2003. The lymphoid past of mouse plasmacytoid cells and thymic dendritic cells. J. Immunol. 170: 4926–4932. 12734335
  32. [34]Izon, D., K. Rudd, W. DeMuth, W.S. Pear, C. Clendenin, R.C. Lindsley, and D. Allman. 2001. A common pathway for dendritic cell and early B cell development. J. Immunol. 167: 1387–1392. 11466357
  33. [35]del Hoyo, G.M., P. Martin, H.H. Vargas, S. Ruiz, C.F. Arias, and C. Ardavin. 2002. Characterization of a common precursor population for dendritic cells. Nature. 415: 1043–1047. 11875574

Cited by

Sorted by citations

Authors
D'Amico, A., & Wu, L.
Affiliations
  • 1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
  • Walter and Eliza Hall Institute of Medical Research (AU)
Corresponding author
Wu, Li
ORCID
Wu, Li
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2003-07-21
Volume
198
Issue
2
Pages
293-303
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20030107
PMC
PMC2194069
OpenAlex
W2115889659
Cited by
386
References
2
Citations by year
2026: 1 · 2025: 8 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 12 · 2019: 11 · 2018: 10 · 2017: 10 · 2016: 9 · 2015: 11 · 2014: 20 · 2013: 27 · 2012: 26
FWCI
9.76
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-sa)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
dendritic cells, plasmacytoid dendritic cells, FLT3, Flt3 ligand, common lymphoid progenitors, common myeloid progenitors, dendritic cell precursors, hematopoiesis, mice
MeSH terms
Animals, Bone Marrow Cells, Dendritic Cells, Hematopoietic Stem Cells, Lymphocytes, Membrane Proteins, Mice, Inbred C57BL, Receptors, Cell Surface, Mice, Knockout, Models, Immunological, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review