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

Author

Listed:
  • Gentaro Izumi

    (National Institute of Environmental Health Sciences, NIH
    University of Tokyo, Hongo, Bunkyo-ku)

  • Hideki Nakano

    (National Institute of Environmental Health Sciences, NIH)

  • Keiko Nakano

    (National Institute of Environmental Health Sciences, NIH)

  • Gregory S. Whitehead

    (National Institute of Environmental Health Sciences, NIH)

  • Sara A. Grimm

    (National Institute of Environmental Health Sciences, NIH)

  • Michael B. Fessler

    (National Institute of Environmental Health Sciences, NIH)

  • Peer W. Karmaus

    (National Institute of Environmental Health Sciences, NIH)

  • Donald N. Cook

    (National Institute of Environmental Health Sciences, NIH)

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.

Suggested Citation

  • Gentaro Izumi & Hideki Nakano & Keiko Nakano & Gregory S. Whitehead & Sara A. Grimm & Michael B. Fessler & Peer W. Karmaus & Donald N. Cook, 2021. "CD11b+ lung dendritic cells at different stages of maturation induce Th17 or Th2 differentiation," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25307-x
    DOI: 10.1038/s41467-021-25307-x
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