Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells
Carlos G. Briseño,
Malay Haldar,
Nicole M. Kretzer,
Xiaodi Wu,
Derek J. Theisen,
Wumesh KC,
Vivek Durai,
Gary E. Grajales-Reyes,
Arifumi Iwata,
Prachi Bagadia,
Theresa L. Murphy,
Kenneth M. Murphy
Affiliations
Carlos G. Briseño
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Malay Haldar
Department of Pathology and Laboratory Medicine, Perelman School of Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Nicole M. Kretzer
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Xiaodi Wu
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Derek J. Theisen
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Wumesh KC
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Vivek Durai
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Gary E. Grajales-Reyes
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Arifumi Iwata
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Prachi Bagadia
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Theresa L. Murphy
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
Kenneth M. Murphy
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA
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-6ChiTREML4− 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-6ChiTREML4+ monocytes were committed to differentiate into Ly-6CloTREML4+ 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.
