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Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β.
Blood. 2014 Oct 09; 124(15):2411-20.Blood

Abstract

The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Here we report that thymic stromal lymphopoietin (TSLP), a keratinocyte-derived cytokine involved in epithelial inflammation, cooperates with transforming growth factor (TGF)-β for the generation of LCs. We show that primary human blood BDCA-1(+), but not BDCA-3(+), dendritic cells (DCs) stimulated with TSLP and TGF-β harbor a typical CD1a(+)Langerin(+) LC phenotype. Electron microscopy established the presence of Birbeck granules, an intracellular organelle specific to LCs. LC differentiation was not observed from tonsil BDCA-1(+) and BDCA-3(+) subsets. TSLP + TGF-β LCs had a mature phenotype with high surface levels of CD80, CD86, and CD40. They induced a potent CD4(+) T-helper (Th) cell expansion and differentiation into Th2 cells with increased production of tumor necrosis factor-α and interleukin-6 compared with CD34-derived LCs. Our findings establish a novel LC differentiation pathway from BDCA-1(+) blood DCs with potential implications in epithelial inflammation. Therapeutic targeting of TSLP may interfere with tissue LC repopulation from circulating precursors.

Authors+Show Affiliations

Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and Centre d 'Investigations Cliniques Institut Gustave Roussy Curie 1428, Paris, France.Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and Centre d 'Investigations Cliniques Institut Gustave Roussy Curie 1428, Paris, France.Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and.Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and.Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and.Department of Biopathology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France; and Centre d 'Investigations Cliniques Institut Gustave Roussy Curie 1428, Paris, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25114264

Citation

Martínez-Cingolani, Carolina, et al. "Human Blood BDCA-1 Dendritic Cells Differentiate Into Langerhans-like Cells With Thymic Stromal Lymphopoietin and TGF-β." Blood, vol. 124, no. 15, 2014, pp. 2411-20.
Martínez-Cingolani C, Grandclaudon M, Jeanmougin M, et al. Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β. Blood. 2014;124(15):2411-20.
Martínez-Cingolani, C., Grandclaudon, M., Jeanmougin, M., Jouve, M., Zollinger, R., & Soumelis, V. (2014). Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β. Blood, 124(15), 2411-20. https://doi.org/10.1182/blood-2014-04-568311
Martínez-Cingolani C, et al. Human Blood BDCA-1 Dendritic Cells Differentiate Into Langerhans-like Cells With Thymic Stromal Lymphopoietin and TGF-β. Blood. 2014 Oct 9;124(15):2411-20. PubMed PMID: 25114264.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β. AU - Martínez-Cingolani,Carolina, AU - Grandclaudon,Maximilien, AU - Jeanmougin,Marine, AU - Jouve,Mabel, AU - Zollinger,Raphaël, AU - Soumelis,Vassili, Y1 - 2014/08/11/ PY - 2014/8/13/entrez PY - 2014/8/13/pubmed PY - 2015/3/4/medline SP - 2411 EP - 20 JF - Blood JO - Blood VL - 124 IS - 15 N2 - The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Here we report that thymic stromal lymphopoietin (TSLP), a keratinocyte-derived cytokine involved in epithelial inflammation, cooperates with transforming growth factor (TGF)-β for the generation of LCs. We show that primary human blood BDCA-1(+), but not BDCA-3(+), dendritic cells (DCs) stimulated with TSLP and TGF-β harbor a typical CD1a(+)Langerin(+) LC phenotype. Electron microscopy established the presence of Birbeck granules, an intracellular organelle specific to LCs. LC differentiation was not observed from tonsil BDCA-1(+) and BDCA-3(+) subsets. TSLP + TGF-β LCs had a mature phenotype with high surface levels of CD80, CD86, and CD40. They induced a potent CD4(+) T-helper (Th) cell expansion and differentiation into Th2 cells with increased production of tumor necrosis factor-α and interleukin-6 compared with CD34-derived LCs. Our findings establish a novel LC differentiation pathway from BDCA-1(+) blood DCs with potential implications in epithelial inflammation. Therapeutic targeting of TSLP may interfere with tissue LC repopulation from circulating precursors. SN - 1528-0020 UR - https://www.unboundmedicine.com/medline/citation/25114264/Human_blood_BDCA_1_dendritic_cells_differentiate_into_Langerhans_like_cells_with_thymic_stromal_lymphopoietin_and_TGF_β_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)39715-9 DB - PRIME DP - Unbound Medicine ER -