The transcription factor C/EBPβ orchestrates dendritic cell maturation and functionality under homeostatic and malignant conditions
Florian Scholz, Michael Grau, Lutz Menzel, Annika Graband, Myroslav Zapukhlyak, Achim Leutz, Martin Janz, Georg Lenz, Armin Rehm, Uta E. Höpken
Abstract
Significance Complex transcription factor networks regulate the development, maturation, and lineage commitment of dendritic cell (DC) subsets. Here, we demonstrate a previously unexpected role of the transcription factor C/EBPβ in murine DC maturation and immunogenic functionality under homeostatic and lymphoma-transformed conditions. Regulated expression of functional C/EBPβ isoforms enables a controlled maturation of DCs. In contrast, the presence of lymphoma cells leads to an up-regulation of C/EBPβ in DCs which transforms them into an immature and protumorigenic subtype. This study also shows that inhibition of the C/EBPβ/mTOR signaling axis abrogates the protumorigenic function of human DCs, suggesting that inhibitors regulating C/EBPβ activity can be used for blocking tumor-promoting functions of DCs in the treatment of hematological neoplasms.