title: Induction of langerin+Langerhans cell-like cells expressing reduced TLR3 from CD34+cord blood cells stimulated with GM-CSF, TGF-β1, and TNF-α.
abstract: Langerhans cells (LCs), a subset of dendritic cells (DCs), reside in body surface presenting antigens from various pathogens and activate immune system after migrating to vicinal lymph nodes. We recently demonstrated that the E-cadherin interaction allowed peripheral blood (PB) CD14+cells to differentiate into LC-like cells that closely resemble primary LCs. Here, with a combination of GM-CSF, TGF-β, and TNF-α, we induced LC-like cells from umbilical cord blood (UCB)derived CD34+cells and compared them with those induced from PB CD14+cells. In contrast to PB CD14+cell-derived LC-like cells with an undetectable surface level of toll-like receptor (TLR)4 and an unresponsiveness feature to bacterial lipopolysaccharide (LPS), CB CD34+cellsderived LC like cells expressed a low, but apparent, surface level of TLR4 and a reduced level of intracellular TLR3. Consistent with this result, they responded to bacterial LPS, but poorly to poly(I:C) reflecting viral RNA. These findings suggest that LC-precursors from circulating PB CD14+cells seem to be arranged in the outer barrier of skin, while LC-precursors from local undifferentiated UCB-derived CD34+cells may be arranged in the inner barrier of mucosal tissues and work together to combat against external pathogens as well as internal malignancies throughout body surface.
authors: Hideko
authors: H
authors: Azuma
authors: Eri
authors: E
authors: Watanabe
authors: Yohei
authors: Y
authors: Otsuka
authors: Yasuyuki
authors: Y
authors: Negishi
authors: Sadayuki
authors: S
authors: Ohkura
authors: Eiji
authors: E
authors: Shinya
authors: Hidemi
authors: H
authors: Takahashi
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D010641:Phenotype; D011247:Pregnancy; D011485:Protein Binding; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; C121916:CD207 protein, human; D015820:Cadherins; D016207:Cytokines; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D037241:Mannose-Binding Lectins; D051196:Toll-Like Receptor 3; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor