Single-cell analyses reveal functional classification of dendritic cells and their potential roles in inflammatory disease

FASEB J. 2019 Mar;33(3):3784-3794. doi: 10.1096/fj.201801489R. Epub 2018 Nov 29.

Abstract

Dendritic cells (DCs) have crucial roles in immune-related diseases. However, it is difficult to explore DCs because of their rareness and heterogeneity. Although previous studies had been performed to detect the phenotypic characteristics of DC populations, the functional diversity has been ignored. Using a combination of flow cytometry, single-cell quantitative PCR, and bioinformatic analysis, we depicted the DC panorama with not only phenotypic but also functional markers. Functional classification of DCs in mouse lymphoid tissue (spleen) and nonlymphoid tissue (liver) was performed. The results revealed that expression of macrophage scavenger receptor 1 ( MSR1) and C-C motif chemokine receptors ( CCR) 1, CCR2, and CCR4 were elevated in liver DCs, suggesting increased lipid uptake and migration abilities. The enriched expression of costimulatory molecule CD80, TLR9, and TLR adaptor MYD88 in spleen DCs indicated a more-mature phenotype, enhanced pathogen recognition, and T-cell stimulation abilities. Furthermore, we compared DCs in the atherosclerotic mouse models with healthy controls. In addition to the quantitative increase in DCs in the liver and spleen of the apolipoprotein E-knockout ( ApoE-/-) mice, the functional expression patterns of the DCs also changed at the single-cell level. These results promote our understanding of the participation of DCs in inflammatory diseases and have potential applications in DC clinical assessment.-Shi, Q., Zhuang, F., Liu, J.-T., Li, N., Chen, Y.-X., Su, X.-B., Yao, A.-H., Yao, Q.-P., Han, Y., Li, S.-S., Qi, Y.-X., Jiang, Z.-L. Single-cell analyses reveal functional classification of dendritic cells and their potential roles in inflammatory disease.

Keywords: antigen-presenting cell; atherosclerotic mouse models; functional heterogeneity; single-cell qPCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology*
  • Flow Cytometry / methods
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, CCR1 / metabolism
  • Scavenger Receptors, Class A / metabolism
  • Single-Cell Analysis / methods
  • Spleen / pathology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • Receptors, CCR1
  • Scavenger Receptors, Class A