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Dendritic cells (DC) in the lung that induce Th17 differentiation remain incompletely understood, in part because conventional CD11b +  DCs (cDC2) are heterogeneous. Here, we report a population of cDCs that rapidly accumulates in lungs of mice following house dust extract inhalation. These cells are Ly-6C + , are developmentally and phenotypically similar to cDC2, and strongly promote Th17 differentiation ex vivo. Single cell RNA-sequencing (scRNA-Seq) of lung cDC2 indicates 5 distinct clusters. Pseudotime analysis of scRNA-Seq data and adoptive transfer experiments with purified cDC2 subpopulations suggest stepwise developmental progression of immature Ly-6C + Ly-6A/E +  cDC2 to mature Ly-6C – CD301b +  lung resident cDC2 lacking  Ccr7  expression, which then further mature into CD200 +  migratory cDC2 expressing  Ccr7 . Partially mature Ly-6C + Ly-6A/E – CD301b –  cDC2, which express  Il1b , promote Th17 differentiation. By contrast, CD200 +  mature cDC2 strongly induce Th2, but not Th17, differentiation. Thus, Th17 and Th2 differentiation are promoted by lung cDC2 at distinct stages of maturation.

CD11b+ lung dendritic cells at different stages of maturation induce Th17 or Th2 differentiation