Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells.
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.
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Carlos G
CG
Briseño
Department of Pathology and Laboratory Medicine, Perelman School of Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Malay
M
Haldar
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Nicole M
NM
Kretzer
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Xiaodi
X
Wu
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Derek J
DJ
Theisen
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Wumesh
W
Kc
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Vivek
V
Durai
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Gary E
GE
Grajales-Reyes
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Arifumi
A
Iwata
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Prachi
P
Bagadia
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Theresa L
TL
Murphy
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.
Kenneth M
KM
Murphy
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000941:Antigens / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D045142:Cross-Priming / Q000187:drug effects / Q000235:genetics*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D050835:Interferon Regulatory Factors / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D000099218:Interferon Regulatory Factor-4
D000941:Antigens; D050976:Basic-Leucine Zipper Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D050835:Interferon Regulatory Factors; D015847:Interleukin-4; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011971:Receptors, Immunologic; D012097:Repressor Proteins; D000099218:Interferon Regulatory Factor-4; C539818:Nr4a1 protein, mouse; C533289:SNFT protein, mouse; C539378:Treml4 protein, mouse