Ontogeny and functional potential of founding dendritic cells in the developing lung

Lung development begins in utero and reaches full maturity post birth. Dendritic cells (DC) play a key role in immune regulation in lungs. However, comprehensive exploration of DCs in these immature lungs has not been performed. Here we explored DCs from fetal to newborn mouse lungs phenotypically, ontogenetically, transcriptomically and functionally and found two DC subsets, resembling adult cDC1 and cDC2, but with key differences. Phenotypically, fetal-cDC1 lacks the classical-DC1 (cDC1) marker XCR1, while the fetal-cDC2 express both cDCassociated genes as well as monocyte-derived DC genes. Both DC subsets wane as lungs enter the alveolar stage, giving way to the more familiar adult cDC1 and cDC2. Both fetal-cDC1 and fetal-cDC2 derive from ED14.5 fetal liver Macrophage Dendritic Progenitors, not from monocytes or classic Precursor-cDC (Pre-cDC), indicating a unique ontogeny of first DCs in developing mouse lungs. Together we provide the first in depth exploration of first DCs in developing lungs.