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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1383-1390. Prepublished online as a Blood First Edition Paper on November 1, 2005; DOI 10.1182/blood-2005-05-1878. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-05-1878v1 107/4/1383    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mende, I. Articles by Merad, M. Search for Related Content PubMed PubMed Citation Articles by Mende, I. Articles by Merad, M. Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Flk2+ myeloid progenitors are the main source of Langerhans cells Ines Mende, Holger Karsunky, Irving L. Weissman, Edgar G. Engleman, and Miriam Merad From the Department of Pathology, Stanford University School of Medicine, Palo Alto, CA. Langerhans cells (LCs) are antigen-presenting cells (APCs) residing in the epidermis that play a major role in skin immunity. Our earlier studies showed that when skin is inflamed LCs are replaced by bone marrow-derived progenitor cells, while during steady-state conditions LCs are able to self-renew in the skin. Identification of the LC progenitors in bone marrow would represent a critical step toward identifying the factors that regulate LC generation as well as their trafficking to the skin. To determine LC lineage origin, we reconstituted lethally irradiated CD45.2 mice with rigorously purified lymphoid and myeloid progenitors from CD45.1 congenic mice. Twenty-four hours later, we exposed the mice to UV light to deplete resident LCs and induce their replacement by progenitors. Reconstitution with common myeloid progenitors (CMPs), common lymphoid progenitors (CLPs), granulocyte-macrophage progenitors (GMPs), or early thymic progenitors led to LC generation within 2 to 3 weeks. CMPs were at least 20 times more efficient at generating LCs than CLPs. LCs from both lineages were derived almost entirely from fetal liver kinase-2+ (Flk-2+) progenitors, displayed typical dendritic-cell (DC) morphology, and showed long-term persistence in the skin. These results indicate that LCs are derived mainly from myeloid progenitors and are dependent on Flt3-ligand for their development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Merad and M. G. Manz Dendritic cell homeostasis Blood, April 9, 2009; 113(15): 3418 - 3427. [Abstract] [Full Text] [PDF] H. Karsunky, M. A. Inlay, T. Serwold, D. Bhattacharya, and I. L. Weissman Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages Blood, June 15, 2008; 111(12): 5562 - 5570. [Abstract] [Full Text] [PDF] J. Bohannon, W. Cui, R. Cox, R. Przkora, E. Sherwood, and T. Toliver-Kinsky Prophylactic Treatment with Fms-Like Tyrosine Kinase-3 Ligand after Burn Injury Enhances Global Immune Responses to Infection J. Immunol., March 1, 2008; 180(5): 3038 - 3048. [Abstract] [Full Text] [PDF] E. Carreras, S. Turner, V. Paharkova-Vatchkova, A. Mao, C. Dascher, and S. Kovats Estradiol Acts Directly on Bone Marrow Myeloid Progenitors to Differentially Regulate GM-CSF or Flt3 Ligand-Mediated Dendritic Cell Differentiation J. Immunol., January 15, 2008; 180(2): 727 - 738. [Abstract] [Full Text] [PDF]

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