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

Carlos G. Briseño | Zendy; Malay Haldar | Zendy; Nicole M. Kretzer | Zendy; Xiaodi Wu | Zendy; Derek J. Theisen | Zendy; Wumesh KC | Zendy; Vivek Durai | Zendy; Gary E. GrajalesReyes | Zendy; Arifumi Iwata | Zendy; Prachi Bagadia | Zendy; Theresa L. Murphy | Zendy; Kenneth M. Murphy | Zendy

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

Author(s) -

Carlos G. Briseño,

Malay Haldar,

Nicole M. Kretzer,

Xiaodi Wu,

Derek J. Theisen,

Wumesh KC,

Vivek Durai,

Gary E. GrajalesReyes,

Arifumi Iwata,

Prachi Bagadia,

Theresa L. Murphy,

Kenneth M. Murphy

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.05.025

Subject(s) - priming (agriculture) , cross presentation , irf4 , monocyte , cd8 , microbiology and biotechnology , dendritic cell , immunology , granulocyte macrophage colony stimulating factor , biology , antigen presentation , t cell , antigen , immune system , cytokine , transcription factor , gene , genetics , botany , germination

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.

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