title: Developmental origin of pre-DC2.
abstract: It is generally accepted that dendritic cells can be generated from either myeloid or lymphoid derived progenitors. Ample information has been collected on the development and nature of myeloid DC type 1 (DC1). In contrast, our current understanding on the origin and function of the lymphoid derived DC type 2 (DC2) is still limited but is increasing rapidly. Here we will summarize recent findings on the developmental origin of the precursor of DC2 (pre-DC2). The presence of pre-DC2 has been revealed in bone marrow, fetal liver, and cord blood, where they develop from hematopoietic stem cells (HSC) most likely via an intermediate pro-DC2 stage. Both in human and mouse, development of pre-DC2 depends on the cytokine FLT3-ligand (FLT3-L). In addition, transcription factors such as Spi-B and members of the basic helix-loop helix (bHLH) family have been shown to be involved in the proper differentiation of HSC into pre-DC2. The human thymus contains a population of cells that closely resembles the peripheral pre-DC2, including interferon (INF)-a production after viral stimulation. Some phenotypic differences have been observed however. Furthermore, we have shown that the thymic microenvironment is able to support development of pre-DC2 from HSC in vivo. A thymus independent pathway of pre-DC2 development exists as well, although at present it is not clear where these extrathymic pre-DC2 are generated. In regard of the absence of a phenotypic defined pro-DC2 population in the thymus, we speculate that development of thymic pre-DC2 may differ from peripheral pre-DC2. The challenge of the near future will be to determine the role of pre-DC2 during thymic T cell development.
authors.affiliation: Division of Immunology, Plesmanlaan 121, Amsterdam, The Netherlands. b.blom@nki.nl
authors.forename: Bianca
authors.initials: B
authors.lastname: Blom
authors.forename: Suzanne J W C
authors.initials: SJ
authors.lastname: Ligthart
authors.forename: Remko
authors.initials: R
authors.lastname: Schotte
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D018801:CD2 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D003713:Dendritic Cells / Q000276:immunology*; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology
chemical_list: D018952:Antigens, CD34; D018801:CD2 Antigens