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Merocytic Dendritic Cells Compose a Conventional Dendritic Cell Subset with Low Metabolic Activity.

Cindy Audiger1,2, Adrien Fois1,2, Alyssa L Thomas3,4

  • 1Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada.

Journal of Immunology (Baltimore, Md. : 1950)
|May 29, 2020
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Summary

Merocytic dendritic cells (mcDCs) are a newly identified dendritic cell subset with potent antigen-presenting cell activity. These cells show characteristics of conventional dendritic cells and could be key to developing novel cancer immunotherapies.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Conventional dendritic cells (cDCs), including cDC1 and cDC2 subsets, are crucial for T cell activation and immune tolerance.
  • A novel dendritic cell (DC) subset, merocytic DCs (mcDCs), has been identified with the unique ability to reverse T cell anergy, suggesting potential in cancer treatment.

Purpose of the Study:

  • To characterize merocytic DCs (mcDCs) and determine their relationship to conventional dendritic cell subsets (cDC1 and cDC2).
  • To investigate the potential of mcDCs in cancer immunotherapy.

Main Methods:

  • Analysis of mcDC expression of the cDC-restricted transcription factor Zbtb46.
  • Assessment of mcDC antigen-presenting cell (APC) activity.
  • Population dynamics studies using reconstitution kinetics and parabiotic mice.
  • Investigation of transcription factor dependency (Irf8, Batf3, Irf4).
  • Transcriptomic analysis and metabolic phenotyping (glucose uptake, glycolysis inhibition).

Main Results:

  • mcDCs express Zbtb46 and exhibit potent APC activity, similar to cDCs.
  • mcDC population dynamics parallel those of cDC1 and cDC2.
  • mcDCs are independent of Irf8 and Batf3 but dependent on Irf4, suggesting a distinct lineage.
  • mcDCs possess a unique transcriptomic signature and a distinct metabolic phenotype with low glucose uptake.
  • mcDC survival is resistant to glycolysis inhibition.

Conclusions:

  • mcDCs represent a distinct cDC subset with unique properties.
  • Their ability to reverse T cell anergy and distinct characteristics offer potential for novel cancer immunotherapies.
  • Identifying human equivalents of mcDCs could advance cancer treatment strategies.