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Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells
Abstract
The ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3 (flt3), also referred to as fetal liver kinase-2 (flk-2), has an important role in hematopoiesis. The flt3 ligand (flt3L) is a growth factor for hematopoietic progenitors and induces hematopoietic progenitor and stem cell mobilization in vivo. In addition, when mice are treated with flt3L immature B cells, natural killer (NK) cells and dendritic cells (DC) are expanded in vivo. To further elucidate the role of flt3L in hematopoiesis, mice lacking flt3L (flt3L−/−) were generated by targeted gene disruption. Leukocyte cellularity was reduced in the bone marrow, peripheral blood, lymph nodes (LN), and spleen. Thymic cellularity, blood hematocrit, and platelet numbers were not affected. Significantly reduced numbers of myeloid and B-lymphoid progenitors were noted in the BM of flt3L−/− mice. In addition a marked deficiency of NK cells in the spleen was noted. DC numbers were also reduced in the spleen, LN, and thymus. Both myeloid-related (CD11c++ CD8−) and lymphoid-related (CD11c++ CD8+) DC numbers were affected. We conclude that flt3L has an important role in the expansion of early hematopoietic progenitors and in the generation of mature peripheral leukocytes.
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Cites
Strain-Dependent Epithelial Defects in Mice Lacking the EGF Receptor
Sibilia, M., & Wagner, E. F. (1995) · Science · doi:10.1126/science.7618085 · Cited by 1,002
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Cited by
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Geissmann, F., Manz, M. G., Jung, S., Sieweke, M. H., Merad, M., & Ley, K. (2010) · Science · doi:10.1126/science.1178331 · Cited by 3,049
Merad, M., Sathe, P., Helft, J., Miller, J., & Mortha, A. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074950 · Cited by 2,309
A natural killer–dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments
Barry, K. C., Hsu, J., Broz, M. L., Cueto, F. J., Binnewies, M., Combes, A. J., Nelson, A. E., Loo, K., Kumar, R., Rosenblum, M. D., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0085-8 · Cited by 1,021
Regulation of Immune Responses by mTOR
Powell, J. D., Pollizzi, K. N., Heikamp, E. B., & Horton, M. R. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075024 · Cited by 836
Cabeza-Cabrerizo, M., Cardoso, A., Minutti, C. M., Pereira da Costa, M., & Reis e Sousa, C. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053707 · Cited by 757
Metadata
- Authors
- McKenna, H. J., Stocking, K. L., Miller, R. E., Brasel, K., De Smedt, T., Maraskovsky, E., Maliszewski, C. R., Lynch, D. H., Smith, J., Pulendran, B., Roux, E. R., Teepe, M., Lyman, S. D., & Peschon, J. J.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2000-06-01
- Volume
- 95
- Issue
- 11
- Pages
- 3489-3497
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W78744612
- Cited by
- 932
- References
- 2
- FWCI
- 13.26
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- McKenna, H. J., Stocking, K. L., Miller, R. E., Brasel, K., De Smedt, T., Maraskovsky, E., Maliszewski, C. R., Lynch, D. H., Smith, J., Pulendran, B., Roux, E. R., Teepe, M., Lyman, S. D., & Peschon, J. J. (2000). Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood. https://doi.org/10.1182/blood.v95.11.3489
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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