First Author | Izumi G | Year | 2021 |
Journal | Nat Commun | Volume | 12 |
Issue | 1 | Pages | 5029 |
PubMed ID | 34413303 | Mgi Jnum | J:316761 |
Mgi Id | MGI:6754015 | Doi | 10.1038/s41467-021-25307-x |
Citation | Izumi G, et al. (2021) CD11b(+) lung dendritic cells at different stages of maturation induce Th17 or Th2 differentiation. Nat Commun 12(1):5029 |
abstractText | 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. |