HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Manfra, D. J. Articles by Lira, S. A. Search for Related Content PubMed PubMed Citation Articles by Manfra, D. J. Articles by Lira, S. A.

Conditional Expression of Murine Flt3 Ligand Leads to Expansion of Multiple Dendritic Cell Subsets in Peripheral Blood and Tissues of Transgenic Mice¹

Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033

The analysis of the development and function of distinct subsets of murine dendritic cells (DC) has been hampered by the limited number of these cells in vivo. To circumvent this limitation we have developed a conditional transgenic mouse model for producing large numbers of DC. We used the tetracycline-inducible system to conditionally express murine Flt3 ligand (FL), a potent hemopoietic growth factor that promotes the differentiation and mobilization of DC. Acute treatment (96 h) of the transgenic animals with the tetracycline analog doxycycline (DOX) promoted an 200-fold increase in serum levels of FL without affecting the number of circulating DC. However, within 1 wk of DOX treatment, the relative number of DC in peripheral blood increased from 8 to 40%. Interestingly, both the levels of FL and the number of DC remained elevated for at least 9 mo with continual DOX treatment. Chronic treatment of the mice with DOX led to dramatic increases in the number of DC in multiple tissues without any apparent pathological consequences. Most DC populations were expanded, including immature and mature DC, myeloid (CD11c⁺CD11b⁺CD8a^-), lymphoid (CD11c⁺CD11b^-CD8a⁺), and the recently defined plasmacytoid (pDC) subsets. Finally, transplantation of BM from green fluorescent protein-expressing mice into lethally irradiated transgenic mice followed by subsequent DOX treatment led to expansion of green fluorescent protein-labeled DC. The transgenic mice described here should thus provide a readily available source of multiple DC subsets and should facilitate the analysis of their role in homeostasis and disease.

This article has been cited by other articles:

				D. Kingston, M. A. Schmid, N. Onai, A. Obata-Onai, D. Baumjohann, and M. G. Manz The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis Blood, July 23, 2009; 114(4): 835 - 843. [Abstract] [Full Text] [PDF]

				A. P. Martin, S. Rankin, S. Pitchford, I. F. Charo, G. C. Furtado, and S. A. Lira Increased Expression of CCL2 in Insulin-Producing Cells of Transgenic Mice Promotes Mobilization of Myeloid Cells From the Bone Marrow, Marked Insulitis, and Diabetes Diabetes, November 1, 2008; 57(11): 3025 - 3033. [Abstract] [Full Text] [PDF]

				Y. Huang, I. J. Fugier-Vivier, T. Miller, M. J. Elliott, H. Xu, L. D. Bozulic, P. M. Chilton, and S. T. Ildstad Plasmacytoid Precursor Dendritic Cells From NOD Mice Exhibit Impaired Function: Are They a Component of Diabetes Pathogenesis? Diabetes, September 1, 2008; 57(9): 2360 - 2370. [Abstract] [Full Text] [PDF]

				G. C. Furtado, B. Pina, F. Tacke, S. Gaupp, N. van Rooijen, T. M. Moran, G. J. Randolph, R. M. Ransohoff, S. W. Chensue, C. S. Raine, et al. A Novel Model of Demyelinating Encephalomyelitis Induced by Monocytes and Dendritic Cells J. Immunol., November 15, 2006; 177(10): 6871 - 6879. [Abstract] [Full Text] [PDF]

				E. Bockamp, C. Antunes, M. Maringer, R. Heck, K. Presser, S. Beilke, S. Ohngemach, R. Alt, M. Cross, R. Sprengel, et al. Tetracycline-controlled transgenic targeting from the SCL locus directs conditional expression to erythrocytes, megakaryocytes, granulocytes, and c-kit-expressing lineage-negative hematopoietic cells Blood, September 1, 2006; 108(5): 1533 - 1541. [Abstract] [Full Text] [PDF]

				R. Pelayo, J. Hirose, J. Huang, K. P. Garrett, A. Delogu, M. Busslinger, and P. W. Kincade Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow Blood, June 1, 2005; 105(11): 4407 - 4415. [Abstract] [Full Text] [PDF]

				T. Tamura, P. Tailor, K. Yamaoka, H. J. Kong, H. Tsujimura, J. J. O'Shea, H. Singh, and K. Ozato IFN Regulatory Factor-4 and -8 Govern Dendritic Cell Subset Development and Their Functional Diversity J. Immunol., March 1, 2005; 174(5): 2573 - 2581. [Abstract] [Full Text] [PDF]

				M. J. Osborn, P. L. Ryan, N. Kirchhof, A. Panoskaltsis-Mortari, F. Mortari, and K.-S. R. S. Tudor Overexpression of murine TSLP impairs lymphopoiesis and myelopoiesis Blood, February 1, 2004; 103(3): 843 - 851. [Abstract] [Full Text] [PDF]

				C. Asselin-Paturel, G. Brizard, J.-J. Pin, F. Briere, and G. Trinchieri Mouse Strain Differences in Plasmacytoid Dendritic Cell Frequency and Function Revealed by a Novel Monoclonal Antibody J. Immunol., December 15, 2003; 171(12): 6466 - 6477. [Abstract] [Full Text] [PDF]