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The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells.

  • Menezes S Laboratory of Phagocyte Immunobiology, King's College London, SE1 1UL London, UK; Centre for Inflammation Biology and Cancer Immunology, King's College London, SE1 1UL London, UK; Peter Gorer Department of Immunobiology, King's College London, SE1 1UL London, UK.
  • Melandri D Laboratory of Phagocyte Immunobiology, King's College London, SE1 1UL London, UK; Centre for Inflammation Biology and Cancer Immunology, King's College London, SE1 1UL London, UK; Peter Gorer Department of Immunobiology, King's College London, SE1 1UL London, UK.
  • Anselmi G Laboratory of Phagocyte Immunobiology, King's College London, SE1 1UL London, UK; Centre for Inflammation Biology and Cancer Immunology, King's College London, SE1 1UL London, UK; Peter Gorer Department of Immunobiology, King's College London, SE1 1UL London, UK.
  • Perchet T Pasteur Institute, 75724 Paris, France.
  • Loschko J The Rockefeller University, New York, NY 10065, USA.
  • Dubrot J Geneva University, 1211 Geneva, Switzerland.
  • Patel R Laboratory of Phagocyte Immunobiology, King's College London, SE1 1UL London, UK; Centre for Inflammation Biology and Cancer Immunology, King's College London, SE1 1UL London, UK; Peter Gorer Department of Immunobiology, King's College London, SE1 1UL London, UK.
  • Gautier EL Pitié-Salpêtrière Hospital, 75013 Paris, France.
  • Hugues S Geneva University, 1211 Geneva, Switzerland.
  • Longhi MP Barts and the London School of Medicine, EC1M 6BQ London, UK.
  • Henry JY University College London, WC1E 6BT London, UK.
  • Quezada SA University College London, WC1E 6BT London, UK.
  • Lauvau G Albert Einstein College of Medicine, New York, NY 10461, USA.
  • Lennon-Duménil AM Institut Curie, 75248 Paris, France.
  • Gutiérrez-Martínez E Laboratory of Phagocyte Immunobiology, King's College London, SE1 1UL London, UK; Centre for Inflammation Biology and Cancer Immunology, King's College London, SE1 1UL London, UK; Peter Gorer Department of Immunobiology, King's College London, SE1 1UL London, UK.
  • Bessis A École Normale Supérieure, 75230 Paris, France.
  • Gomez-Perdiguero E Pasteur Institute, 75724 Paris, France.
  • Jacome-Galarza CE Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Garner H Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Geissmann F Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Golub R Pasteur Institute, 75724 Paris, France.
  • Nussenzweig MC The Rockefeller University, New York, NY 10065, USA.
  • Guermonprez P Laboratory of Phagocyte Immunobiology, King's College London, SE1 1UL London, UK; Centre for Inflammation Biology and Cancer Immunology, King's College London, SE1 1UL London, UK; Peter Gorer Department of Immunobiology, King's College London, SE1 1UL London, UK. Electronic address: pierre.guermonprez@kcl.ac.uk.
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  • 2016-12-22
Published in:
  • Immunity. - 2016
GM-CSF
PU.1 transcription factor
macrophages
monocyte-derived dendritic cells
monocytes
Adoptive Transfer
Animals
Antigens, Ly
Cell Differentiation
Cell Separation
Dendritic Cells
Flow Cytometry
Macrophages
Mice
Monocytes
Nitric Oxide Synthase Type II
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
English Inflammation triggers the differentiation of Ly6Chi monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3+CD11c-MHCII+PU.1hi subset. This subset acted as a precursor for FcγRIII+PD-L2+CD209a+, GM-CSF-dependent moDCs but was distal from the DC lineage, as shown by fate-mapping experiments using Zbtb46. By contrast, Flt3-CD11c-MHCII-PU.1lo monocytes differentiated into FcγRIII+PD-L2-CD209a-iNOS+ macrophages upon microbial stimulation. Importantly, Sfpi1 haploinsufficiency genetically distinguished the precursor activities of monocytes toward moDCs or microbicidal macrophages. Indeed, Sfpi1+/- mice had reduced Flt3+CD11c-MHCII+ monocytes and GM-CSF-dependent FcγRIII+PD-L2+CD209a+ moDCs but generated iNOS+ macrophages more efficiently. Therefore, intercellular disparities of PU.1 expression within naive monocytes segregate progenitor activity for inflammatory iNOS+ macrophages or moDCs.
Language
  • English
Open access status
hybrid
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Persistent URL
https://folia.unifr.ch/global/documents/232656
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