PMID- 16037408 OWN - NLM STAT- MEDLINE DCOM- 20060110 LR - 20220309 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 78 IP - 4 DP - 2005 Oct TI - A novel role for Notch ligand Delta-1 as a regulator of human Langerhans cell development from blood monocytes. PG - 921-9 AB - Human Langerhans cells (LCs) are of hematopoietic origin, but cytokine regulation of their development is not fully understood. Notch ligand Delta-1 is expressed in a proportion of the skin. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta1 (TGF-beta1) are also secreted in the skin. We report here that Delta-1, in concert with GM-CSF and TGF-beta1, induces the differentiation of human CD14(+) blood monocytes into cells that express LC markers: CD1a, Langerin, cutaneous lymphocyte-associated antigen, CC chemokine receptor 6, E-cadherin, and Birbeck granules. The resulting cells display phagocytic activity and chemotaxis to macrophage inflammatory protein-1alpha (MIP-1alpha). In response to CD40 ligand and tumor necrosis factor alpha, the cells acquire a mature phenotype of dendritic cells that is characterized by up-regulation of human leukocyte antigen (HLA)-ABC, HLA-DR, CD80, CD86, CD40, and CD54 and appearance of CD83. These cells in turn show chemotaxis toward MIP-1beta and elicit activation of CD8(+) T cells and T helper cell type 1 polarization of CD4(+) T cells. Thus, blood monocytes can give rise to LCs upon exposure to the skin cytokine environment consisting of Delta-1, GM-CSF, and TGF-beta1, which may be, in part, relevant to the development of human epidermal LCs. Our results extend the functional scope of Notch ligand delta-1 in human hematopoiesis. FAU - Hoshino, Natsuki AU - Hoshino N AD - Department of Hematology and Oncology, Mie University School of Medicine, Mie 514-8507, Japan. n-kata@clin.medic.mie-u.ac.jp FAU - Katayama, Naoyuki AU - Katayama N FAU - Shibasaki, Tetsunori AU - Shibasaki T FAU - Ohishi, Kohshi AU - Ohishi K FAU - Nishioka, Junji AU - Nishioka J FAU - Masuya, Masahiro AU - Masuya M FAU - Miyahara, Yoshihiro AU - Miyahara Y FAU - Hayashida, Masahiko AU - Hayashida M FAU - Shimomura, Daiki AU - Shimomura D FAU - Kato, Takuma AU - Kato T FAU - Nakatani, Kaname AU - Nakatani K FAU - Nishii, Kazuhiro AU - Nishii K FAU - Kuribayashi, Kagemasa AU - Kuribayashi K FAU - Nobori, Tsutomu AU - Nobori T FAU - Shiku, Hiroshi AU - Shiku H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050721 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Enzyme Inhibitors) RN - 0 (Homeodomain Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Ligands) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Membrane Proteins) RN - 0 (TGFB1 protein, human) RN - 0 (Transcription Factor HES-1) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 0 (delta protein) RN - 149348-15-2 (HES1 protein, human) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.- (Endopeptidases) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.46 (BACE1 protein, human) SB - IM MH - Amyloid Precursor Protein Secretases MH - Aspartic Acid Endopeptidases MH - Basic Helix-Loop-Helix Transcription Factors/drug effects/genetics MH - CD8-Positive T-Lymphocytes/metabolism MH - Cell Differentiation/drug effects/physiology MH - Cell Polarity/physiology MH - Cells, Cultured MH - Chemotaxis/physiology MH - Endopeptidases/drug effects MH - Enzyme Inhibitors/pharmacology MH - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism/pharmacology MH - Homeodomain Proteins/drug effects/genetics MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Langerhans Cells/*cytology/drug effects/*physiology MH - Ligands MH - Lipopolysaccharide Receptors/*blood/drug effects/metabolism MH - Membrane Proteins/pharmacology/*physiology MH - Monocytes/*cytology/drug effects/*physiology MH - Phenotype MH - Transcription Factor HES-1 MH - Transforming Growth Factor beta/metabolism/pharmacology MH - Transforming Growth Factor beta1 EDAT- 2005/07/23 09:00 MHDA- 2006/01/13 09:00 CRDT- 2005/07/23 09:00 PHST- 2005/07/23 09:00 [pubmed] PHST- 2006/01/13 09:00 [medline] PHST- 2005/07/23 09:00 [entrez] AID - jlb.1204746 [pii] AID - 10.1189/jlb.1204746 [doi] PST - ppublish SO - J Leukoc Biol. 2005 Oct;78(4):921-9. doi: 10.1189/jlb.1204746. Epub 2005 Jul 21.