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

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

Author information

1
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
2
Department of Pathology and Laboratory Medicine, Perelman School of Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; Howard Hughes Medical Institute, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address: kmurphy@wustl.edu.

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.

PMID:
27264183
PMCID:
PMC4941620
DOI:
10.1016/j.celrep.2016.05.025
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no competing financial interests.

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