Ontogeny and functional potential of founding dendritic cells in the developing lung
Radika Soysa1, Saajidah Abideen1, Victor Zepeda Reyes1
1Translation Science and Therapeutic Division, Fred Hutchinson Cancer Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Biorxiv : the Preprint Server for Biology
|November 19, 2025
Summary
This study reveals unique dendritic cell (DC) subsets in developing mouse lungs, differing from adult types. These early lung DCs originate from fetal liver progenitors, highlighting a distinct developmental pathway for lung immunity.
Area of Science:
- Immunology
- Developmental Biology
- Pulmonology
Background:
- Dendritic cells (DCs) are crucial for lung immune regulation.
- Immune cell development in immature lungs remains underexplored.
- Understanding early lung immunity is vital for addressing neonatal respiratory conditions.
Purpose of the Study:
- To comprehensively characterize dendritic cells (DCs) in fetal and newborn mouse lungs.
- To investigate the phenotype, ontogeny, transcriptome, and function of early lung DCs.
- To compare these DCs with their adult counterparts and elucidate their developmental origins.
Main Methods:
- Phenotypic analysis of DCs using cell surface markers.
- Transcriptomic profiling to identify gene expression patterns.
- Functional assays to assess DC capabilities.
- Tracing ontogeny from progenitor cells in fetal mouse lungs.
Main Results:
- Identified two distinct fetal DC subsets, resembling but differing from adult classical DC1 (cDC1) and cDC2.
- Fetal-cDC1 lacked the XCR1 marker, while fetal-cDC2 expressed both cDC and monocyte-derived DC genes.
- These fetal DC subsets diminished as lungs matured, replaced by adult cDC1 and cDC2.
- Fetal DCs originated from fetal liver Macrophage Dendritic Progenitors, not monocytes or Precursor-cDC (Pre-cDC).
Conclusions:
- The first dendritic cells in developing mouse lungs possess unique characteristics and ontogeny.
- These findings provide novel insights into the early immune system development within the lung.
- This research lays the groundwork for understanding lung immune responses from birth.
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