The Heterogeneity of Ly6Chi Monocytes Controls Their Differentiation into iNOS+ Macrophages or Monocyte-Derived Dendritic Cells
| Autor: | Ana-Maria Lennon-Duménil, Enrique Gutiérrez-Martinez, Stéphanie Hugues, Grégoire Lauvau, Hannah Garner, Jakob Loschko, Emmanuel L. Gautier, Rachel Golub, Jake Y. Henry, Elisa Gomez-Perdiguero, Shinelle Menezes, Frederic Geissmann, M. Paula Longhi, Daisy Melandri, Christian E. Jacome-Galarza, Alain Bessis, Pierre Guermonprez, Thibaut Perchet, Giorgio Anselmi, Juan Dubrot, Sergio A. Quezada, Rajen Patel, Michel C. Nussenzweig |
|---|---|
| Přispěvatelé: | Centre for Cellular and Molecular Biology of Inflammation, King‘s College London, Peter Gorer Department of Immunobiology, laboratory of phagocyte immunobiology, Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rockefeller University [New York], University of Geneva [Switzerland], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Barts and the London Medical School, University College of London [London] (UCL), Albert Einstein College of Medicine [New York], Institut Curie [Paris], École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL), Memorial Sloane Kettering Cancer Center [New York], The research was supported by the MRC (MR/K01241X/1), BBSRC (BB/M0297351) and King’s Health partners., Rockefeller University, CHU Pitié-Salpêtrière [APHP], Albert Einstein College of Medicine, Institut Curie, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Genève = University of Geneva (UNIGE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École normale supérieure - Paris (ENS-PSL) |
| Rok vydání: | 2016 |
| Předmět: |
Nitric Oxide Synthase Type II/immunology
0301 basic medicine Adoptive cell transfer Ly/immunology [SDV]Life Sciences [q-bio] Cellular differentiation Nitric Oxide Synthase Type II Stimulation Cell Separation ddc:616.07 Polymerase Chain Reaction Cell Differentiation/immunology Mice 0302 clinical medicine Antigens Ly Immunology and Allergy Oligonucleotide Array Sequence Analysis medicine.diagnostic_test Cell Differentiation Flow Cytometry Adoptive Transfer macrophages Cell biology Infectious Diseases medicine.anatomical_structure [SDV.IMM]Life Sciences [q-bio]/Immunology medicine.symptom monocytes Intracellular Macrophages/cytology/immunology monocyte-derived dendritic cells Immunology Inflammation Biology Dendritic Cells/cytology/immunology Article Flow cytometry PU.1 transcription factor 03 medical and health sciences TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY medicine Animals Antigens Monocytes/cytology/immunology Progenitor Monocyte GM-CSF Dendritic Cells 030104 developmental biology 030215 immunology |
| Zdroj: | Immunity Immunity, Elsevier, 2016, 45 (6), pp.1205-1218. ⟨10.1016/j.immuni.2016.12.001⟩ Immunity, Vol. 45, No 6 (2016) pp. 1205-1218 Immunity, 2016, 45 (6), pp.1205-1218. ⟨10.1016/j.immuni.2016.12.001⟩ Menezes, S, Melandri, D, Anselmi, G, Perchet, T, Loschko, J, Dubrot, J, Patel, R, Gautier, E L, Hugues, S, Longhi, M P, Henry, J Y, Quezada, S A, Lauvau, G, Lennon-Duménil, A M, Gutiérrez-Martínez, E, Bessis, A, Gomez-Perdiguero, E, Jacome-Galarza, C E, Garner, H, Geissmann, F, Golub, R, Nussenzweig, M C & Guermonprez, P 2016, ' The Heterogeneity of Ly6C hi Monocytes Controls Their Differentiation into iNOS + Macrophages or Monocyte-Derived Dendritic Cells ', Immunity, vol. 45, no. 6, pp. 1205-1218 . https://doi.org/10.1016/j.immuni.2016.12.001 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2016.12.001 |
| Popis: | Summary 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. Graphical Abstract Highlights • Murine Ly6ChiCD115+ monocytes are heterogeneous • DC-related genes (Cd209a and MHCII) are expressed in a subset of FcγRIII+ monocytes • GM-CSF-dependent CD209a+ moDCs are generated by FcγRIII+CD209a+MHCII+ monocytes • iNOS+ macrophages are generated by FcγRIII+CD209a−MHCII− monocytes Monocytes can differentiate into multiple progenies during inflammation. Here, Menezes et al. show that monocytes from naive mice are heterogeneous and contain distinct precursor subsets giving rise to iNOS+ inflammatory macrophages or GM-CSF-induced CD209a+ monocyte-derived dendritic cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|