Development of pulmonary dendritic cells and macrophage subsets (Homo sapiens)

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1HSCCMPMDPcMoPLy6C-hiMonocytesCDPPre-cDCPre-cDCPre-cDCPre-cDC2Pre-pDCpDCpDCPre-cDC1Pre-cDC1Pre-cDC1HSC: Hematopoietic stem cellsYolksacMDP: Monocyte-macrophage DC progenitorcMoP: Common monocyte progenitorPathways found in independent studiescDC: Conventional DCCMP: Common myeloid progenitorCDP: Common DC progenitorFetalliverID2IRF4RUNX2FLT3LIkarosSTAT3IRF8CSF2PU.1TPOPU.1IRF8CSF1CSF1FLT3LPU.1CSF1STAT3FLT3LPU.1STAT3PU.1E2-2FLT3LFLT3LCSF1IRF8BATF3Pre-cDC2Pre-cDC2Ly6C-loMonocytesLy6C-hiMonocytesLy6C-hiMonocytesLy6C-loMonocytesLy6C-loMonocytesCSF1CD103+ DCIRF8BATF3CD11b+ DCFLT3LIRF4CSF1CSF2CD103+Monocyte-derived DCMonocyte-derivedmacrophageCD11b+ Monocyte-derivedmacrophageLy6C-loMonocytesLy6C-loMonocytesAlveolarmacrophageLungInterstitialmacrophageBloodBone MarrowPathways found in single study / controversialDC: Dendritic cellspDC: Plasmacytoid DC


Description

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 CPTAC Assay Portal

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Bibliography

  1. Hoffmann F, Ender F, Schmudde I, Lewkowich IP, Köhl J, König P, Laumonnier Y; ''Origin, Localization, and Immunoregulatory Properties of Pulmonary Phagocytes in Allergic Asthma.''; Front Immunol, 2016 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
129336view09:10, 27 March 2024MkutmonOntology Term : 'regulatory pathway' added !
129221view02:09, 16 March 2024EweitzOntology Term : 'hematopoietic stem cell' added !
129220view02:08, 16 March 2024EweitzOntology Term : 'common dendritic progenitor' added !
129219view02:07, 16 March 2024EweitzOntology Term : 'common myeloid progenitor' added !
129218view02:06, 16 March 2024EweitzOntology Term : 'plasmacytoid dendritic cell, human' added !
129217view02:06, 16 March 2024EweitzOntology Term : 'plasmacytoid dendritic cell' added !
120069view18:43, 27 October 2021Khanspersupdated interactions to graphical lines
106387view21:24, 28 August 2019KhanspersModified description
105569view06:26, 9 August 2019KhanspersModified description
89703view20:56, 26 September 2016KhanspersConnected interaction
89699view19:16, 26 September 2016Khanspersincreased cell label font size
89698view19:08, 26 September 2016Khanspersupdated colors for readability
89319view15:45, 1 September 2016KhanspersOntology Term : 'bone marrow hematopoietic cell' added !
89318view15:44, 1 September 2016KhanspersOntology Term : 'dendritic cell' added !
89317view15:44, 1 September 2016KhanspersOntology Term : 'macrophage dendritic cell progenitor' added !
89316view15:43, 1 September 2016KhanspersModified description
89314view15:40, 1 September 2016KhanspersNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
BATF3GeneProductENSG00000123685 (Ensembl)
CSF1GeneProductENSG00000184371 (Ensembl)
CSF2GeneProductENSG00000164400 (Ensembl)
E2-2GeneProductENSG00000196628 (Ensembl)
FLT3LGeneProductENSG00000090554 (Ensembl)
ID2GeneProductENSG00000115738 (Ensembl)
IRF4GeneProductENSG00000137265 (Ensembl)
IRF8GeneProductENSG00000140968 (Ensembl)
IkarosGeneProductENSG00000185811 (Ensembl)
PU.1GeneProductENSG00000066336 (Ensembl)
RUNX2GeneProductENSG00000124813 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
TPOGeneProductENSG00000115705 (Ensembl)

Annotated Interactions

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