title: Preferential Langerhans cell differentiation from CD34(+) precursors upon introduction of ABCG2 (BCRP).
abstract: Epidermal Langerhans cells (LC) and dermal interstitial dendritic cells (IDC) were found to express the ATP-binding cassette (ABC) transporter breast cancer resistance protein (BCRP; ABCG2). Also, low BCRP expression was present on CD34(+) blood DC precursors and expression was increased upon their differentiation to LC. The CD34(+) acute myeloid leukemia-derived DC cell line MUTZ3 can be cultured into LC or IDC, depending on the cytokine cocktail used. Introduction of functional BCRP in MUTZ3 progenitor cells through retroviral transduction resulted in the emergence of typical LC-characteristics in IDC cultures; the majority of cells remained negative for the IDC-specific C-type lectin DC-SIGN, but rather displayed enhanced expression of the LC-specific C-type lectin Langerin and characteristic high expression levels of CD1a. BCRP-induced skewing toward LC-like differentiation coincided with early RelB expression in 'IDC', derived from MUTZ3-BCRP, and depended on endogenous transforming growth factor beta (TGF-β) production. Intriguingly, cellular BCRP localization differed between skin LC and IDC, and a more cytoplasmic BCRP localization, as observed in primary skin LC, seemed to relate to LC-like differentiation in IDC cultures upon BCRP introduction in MUTZ3 progenitors. Together these data support a role for BCRP in preferential LC differentiation from CD34(+) myeloid DC progenitors.
authors: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Rieneke
authors: R
authors: van de Ven
authors: Jelle J
authors: JJ
authors: Lindenberg
authors: Anneke W
authors: AW
authors: Reurs
authors: Rik J
authors: RJ
authors: Scheper
authors: George L
authors: GL
authors: Scheffer
authors: Tanja D
authors: TD
authors: de Gruijl
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D018949:Antigens, CD1 / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001943:Breast Neoplasms; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute; D009363:Neoplasm Proteins / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D051841:Transcription Factor RelB / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D018949:Antigens, CD1; D018952:Antigens, CD34; D037181:Lectins, C-Type; D009363:Neoplasm Proteins; C497593:RELB protein, human; D016212:Transforming Growth Factor beta; D051841:Transcription Factor RelB