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Publication : CD11b<sup>+</sup> lung dendritic cells at different stages of maturation induce Th17 or Th2 differentiation.

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.
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