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, K. C. Wumesh, Vivek Durai, Gary E. Grajales-Reyes, Arifumi Iwata, Prachi Bagadia, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

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-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.

Original languageEnglish
Pages (from-to)2462-2474
Number of pages13
JournalCell Reports
Volume15
Issue number11
DOIs
StatePublished - Jun 14 2016

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