Dendritic Cell and Macrophage Nomenclature and ClassificationFlorent Ginhoux, Martin Guilliams, Shalin Naik The mononuclear phagocyte system (MPS) comprises dendritic cells (DCs), monocytes and macrophages (MØs) that together play crucial roles in tissue immunity and homeostasis, but also contribute to a broad spectrum of pathologies. They are thus attractive therapeutic targets for immune therapy. However, the distinction between DCs, monocytes and MØ subpopulations has been a matter of controversy and the current nomenclature has been a confounding factor. DCs are remarkably heterogeneous and consist of multiple subsets traditionally defined by their expression of various surface markers. While markers are important to define various populations of the MPS, they do not specifically define the intrinsic nature of a cell population and do not always segregate a bona fide cell type of relative homogeneity. Markers are redundant, or simply define distinct activation states within one subset rather than independent subpopulations. One example are the steady-state CD11b+ DCs which are often not distinguished from monocytes, monocyte-derived cells, and macrophages due to their overlapping phenotype. Lastly, monocyte fate during inflammation results in cells bearing the phenotypic and functional features of both DCs and MØs significantly adding to the confusion. In fact, depending on the context of the study and the focus of the laboratory, a monocyte-derived cell will be either be called "monocyte-derived DCs" or "macrophages". Because the names we give to cells are often associated with a functional connotation, this is much more than simple semantics. The "name" we give to a population fundamentally changes the perception of its biology and can impact on research design and interpretation. Recent evidence in the ontogeny and transcriptional regulation of DCs and MØs, combined with the identification of DC- and MØ-specific markers has dramatically changed our understanding of their interrelationship in the steady state and inflammation. In steady state, DCs are constantly replaced by circulating blood precursors that arise from committed progenitors in the bone marrow. Similarly, some MØ populations are also constantly replaced by circulating blood monocytes. However, others tissue MØs are derived from embryonic precursors, are seeded before birth and maintain themselves in adults by self-renewal. In inflammation, such differentiation pathways are fundamentally changed and unique monocyte-derived inflammatory cells are generated. Current DC, monocyte and MØ nomenclature does not take into account these new developments and as a consequence is quite confusing. We believe that the field is in need of a fresh view on this topic as well as an upfront debate on DC and MØ nomenclature. Our aim is to bring expert junior and senior scientists to revisit this topic in light of these recent developments. This Research Topic will cover all aspects of DC, monocyte and MØ biology including development, transcriptional regulation, functional specializations, in lymphoid and non-lymphoid tissues, and in both human and mouse models. Given the central position of DCs, monocytes and MØs in tissue homeostasis, immunity and disease, this topic should be of interest to a large spectrum of the biomedical community. |
Contents
Dendritic Cell and Macrophage Nomenclature and Classification | 6 |
From the reticuloendothelial to mononuclear phagocyte system the unaccounted years | 8 |
Whats in a name? Some early and current issues in dendritic cell nomenclature | 15 |
practical implementation of a novel mononuclear phagocyte classification system | 19 |
Ontogeny of tissueresident macrophages | 31 |
Transcriptional regulation of mononuclear phagocyte development | 45 |
Fate mapping of dendritic cells | 56 |
The debate about dendritic cells and macrophages in the kidney | 71 |
heterogeneity development and function | 95 |
The complex myeloid network of the liver with diverse functional capacity at steady state and in inflammation | 104 |
a tale of two species? | 115 |
Defining mononuclear phagocyte subset homology across several distant warmblooded vertebrates through comparative transcriptomics | 130 |
Investigating evolutionary conservation of dendritic cell subset identity and functions | 156 |
established features and open questions | 173 |
The known unknowns of the human dendritic cell network | 178 |
A systematic approach to identify markers of distinctly activated human macrophages | 185 |
Guardians of the gut murine intestinal macrophages and dendritic cells | 78 |
Microglia versus myeloid cell nomenclature during brain inflammation | 88 |
Common terms and phrases
adult analysis antigen Batf3 Biol bone marrow CD8+ cDC1 cDC2 cell types chemokine conserved cross-presentation cytokine DC subsets defined dendritic cell development dendritic cell subsets dendritic cells developmental differentiation disease distinct embryonic etal fate mapping fetal monocytes fibrosis Figure flow cytometry Flt3 FLT3L gene expression profiles Ginhoux F GM-CSF Greter Guilliams hematopoietic stem cells homeostasis homology HSCs human and mouse identified Immunology induce infection inflammation inflammatory intestinal IRF4 Irf8 Kupffer cells lamina propria Langerhans cells lineage liver LPMs lymph nodes macrophage activation macrophage populations macrophages mice microglia Mo/MP MoDC molecular monocyte-derived cells monocytes mononuclear phagocyte subsets murine myeloid cells Nat Immunol Nat Rev Immunol nomenclature ontogeny origin pathways peritoneal peritoneal macrophages phenotype plasmacytoid dendritic cells potential precursors progenitors receptor regulated renal responses role sheep signature species spleen SPMs studies surface markers tissue macrophages tissue-resident macrophages transcription factor vitro vivo XCR1