Development of pulmonary dendritic cells and macrophage subsets (WP3892)

Homo sapiens

Development of pulmonary DC and macrophage subsets. This model of pulmonary DC and macrophage subset differentiation in mice summarizes recent findings suggesting early lineage commitment of cDCs in the BM and differentiation of monocytes into different population with DC, macrophage, or suppressive functions. All DC subsets present in the lung originate from hematopoietic progenitors (HSC) that differentiate into a common myeloid progenitor (CMP). Such CMPs further differentiate to a common DC progenitors (CDPs) or macrophage DC progenitors (MDPs). MDPs give rise to a common monocyte precursor (cMoP). In a CSF-1-dependent mechanism, Ly6Chi monocytes develop, which can further differentiate into Ly6Clo monocytes. Such Ly6Clo monocytes may also derive directly from cMoPs. Both monocyte populations can enter the lung and become monocyte-derived DCs, macrophages, or suppressor cells (25, 62). CDPs also serve as precursors for pDCs and pre-cDCs. Recent studies suggest that the two cDC populations deriving from the pre-cDC progenitor, i.e., CD103+ cDCs and CD11b+ cDCs, arise already in the bone marrow as pre-cDC1/cDC2 subtypes. One study suggested that pulmonary monocytes may differentiate into pulmonary CD103+ and CD11b+ DC; however, it is unclear whether such cells are phenotypically and functionally identical to CD103+ and CD11b+ cDCs. Activation of defined transcription factors (in blue) at distinct time points is critical for lineage commitment of the different DC precursors. During the early developmental stages, important transcription factors include STAT3, IRF8, and PU.1. At later stages, E2-2 is decisive for pDC commitment of CDPs. BATF3 and IRF8 are associated with the CD103+ cDC and IRF4 with the CD11b+ differentiation. In addition to the transcription factors, several growth factors (in green) play key functions in the development of pre-cDCs and the different DC subsets, in particular Flt3L, CSF-1 (M-CSF), and CSF-2 (GM-CSF). The lung contains two major macrophage populations, i.e., alveolar and interstitial macrophages (AMs and IMs, respectively). It is now well appreciated that AMs derive from yolk sac and fetal liver progenitors that colonize the embryonic lung and are maintained by self-renewal at steady state. The origin of IMs remains elusive. Some data suggest that they represent monocyte-derived macrophages. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3892 CPTAC Assay Portal]

Authors

Kristina Hanspers , Eric Weitz , and Martina Summer-Kutmon

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

regulatory pathway

Cell Type Ontology

macrophage dendritic cell progenitor plasmacytoid dendritic cell, human plasmacytoid dendritic cell bone marrow hematopoietic cell common myeloid progenitor common dendritic progenitor hematopoietic stem cell dendritic cell

Participants

Label Type Compact URI Comment
ID2 GeneProduct ensembl:ENSG00000115738
IRF4 GeneProduct ensembl:ENSG00000137265
RUNX2 GeneProduct ensembl:ENSG00000124813
FLT3L GeneProduct ensembl:ENSG00000090554
Ikaros GeneProduct ensembl:ENSG00000185811
STAT3 GeneProduct ensembl:ENSG00000168610
IRF8 GeneProduct ensembl:ENSG00000140968
CSF2 GeneProduct ensembl:ENSG00000164400
PU.1 GeneProduct ensembl:ENSG00000066336
TPO GeneProduct ensembl:ENSG00000115705
CSF1 GeneProduct ensembl:ENSG00000184371
E2-2 GeneProduct ensembl:ENSG00000196628
BATF3 GeneProduct ensembl:ENSG00000123685

References

  1. Origin, Localization, and Immunoregulatory Properties of Pulmonary Phagocytes in Allergic Asthma. Hoffmann F, Ender F, Schmudde I, Lewkowich IP, Köhl J, König P, et al. Front Immunol. 2016 Mar 23;7:107. PubMed Europe PMC Scholia