Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells

Cell Rep. 2016 Jun 14;15(11):2462-74. doi: 10.1016/j.celrep.2016.05.025. Epub 2016 Jun 2.

Abstract

Both classical DCs (cDCs) and monocyte-derived DCs (Mo-DCs) are capable of cross-priming CD8(+) T cells in response to cell-associated antigens. We found that Ly-6C(hi)TREML4(-) monocytes can differentiate into Zbtb46(+) Mo-DCs in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) but that Ly-6C(hi)TREML4(+) monocytes were committed to differentiate into Ly-6C(lo)TREML4(+) monocytes. Differentiation of Zbtb46(+) Mo-DCs capable of efficient cross-priming required both GM-CSF and IL-4 and was accompanied by the induction of Batf3 and Irf4. However, monocytes require IRF4, but not BATF3, to differentiate into Zbtb46(+) Mo-DCs capable of cross-priming CD8(+) T cells. Instead, Irf4(-/-) monocytes differentiate into macrophages in response to GM-CSF and IL-4. Thus, cDCs and Mo-DCs require distinct transcriptional programs of differentiation in acquiring the capacity to prime CD8(+) T cells. These differences may be of consideration in the use of therapeutic DC vaccines based on Mo-DCs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / metabolism
  • Antigens / metabolism
  • Basic-Leucine Zipper Transcription Factors / deficiency
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / drug effects
  • Cell Lineage / drug effects
  • Cross-Priming / drug effects
  • Cross-Priming / genetics*
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Interferon Regulatory Factors / metabolism
  • Interleukin-4 / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / cytology*
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism
  • Receptors, Immunologic / metabolism
  • Repressor Proteins / deficiency
  • Repressor Proteins / metabolism
  • Signal Transduction / drug effects
  • Transcription, Genetic* / drug effects

Substances

  • Antigens
  • Basic-Leucine Zipper Transcription Factors
  • Interferon Regulatory Factors
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptors, Immunologic
  • Repressor Proteins
  • SNFT protein, mouse
  • Treml4 protein, mouse
  • interferon regulatory factor-4
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor