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

ABSTRACT: 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.

SUBMITTER: Izumi G 

PROVIDER: S-EPMC8377117 | biostudies-literature |

REPOSITORIES: biostudies-literature