Dendritic cell (DC) maturation is a prerequisite for the induction of adaptive immune responses against pathogens and cancer. Transcription factor (TF) networks control differential aspects of early DC progenitor versus late-stage DC cell fate decisions. Here, we identified the TF C/EBPβ as a key regulator for DC maturation and immunogenic functionality under homeostatic and lymphoma-transformed conditions. Upon cell-specific deletion of C/EBPβ in CD11c⁺MHCII^hi DCs, gene expression profiles of splenic C/EBPβ^−/− DCs showed a down-regulation of E2F cell cycle target genes and associated proliferation signaling pathways, whereas maturation signatures were enriched. Total splenic DC cell numbers were modestly increased but differentiation into cDC1 and cDC2 subsets were unaltered. The splenic CD11c⁺MHCII^hiCD64⁺ DC compartment was also increased, suggesting that C/EBPβ deficiency favors the expansion of monocytic-derived DCs. Expression of C/EBPβ could be mimicked in LAP/LAP* isoform knockin DCs, whereas the short isoform LIP supported a differentiation program similar to deletion of the full-length TF. In accordance with E2F1 being a negative regulator of DC maturation, C/EBPβ^−/− bone marrow-derived DCs matured much faster enabling them to activate and polarize T cells stronger. In contrast to a homeostatic condition, lymphoma-exposed DCs exhibited an up-regulation of the E2F transcriptional pathways and an impaired maturation. Pharmacological blockade of C/EBPβ/mTOR signaling in human DCs abrogated their protumorigenic function in primary B cell lymphoma cocultures. Thus, C/EBPβ plays a unique role in DC maturation and immunostimulatory functionality and emerges as a key factor of the tumor microenvironment that promotes lymphomagenesis.

树突状细胞（DC）的成熟是诱导针对病原体和癌症的适应性免疫反应的先决条件。转录因子（TF）网络控制早期DC祖细胞与晚期DC细胞命运决定的不同方面。在这里，我们确定了TF C /EBPβ是稳态和淋巴瘤转化条件下DC成熟和免疫原性功能的关键调节剂。一旦细胞特异性缺失C /EBPβ在的CD11c ⁺ MHCII^喜的DC，脾的C基因表达谱/EBPβ ^{- / -}DCs显示出E2F细胞周期靶基因和相关的增殖信号通路的下调，而成熟的信号被丰富。总脾DC细胞数量适度增加，但分化为cDC1和cDC2子集不变。脾脏CD11c ⁺ MHCII ^hi CD64 ⁺ DC区室也增加，表明C /EBPβ缺乏促进单核细胞衍生DC的扩增。C /EBPβ的表达可以在LAP / LAP *同工型敲入DC中进行模拟，而短同工型LIP支持类似于全长TF缺失的分化程序。根据E2F1是DC成熟的负调节器，C /EBPβ ^-/-骨髓来源的DC的成熟速度要快得多，从而使它们能够更强地激活和极化T细胞。与体内平衡状态相反，暴露于淋巴瘤的DC表现出E2F转录途径的上调和成熟受损。在人DC中C /EBPβ/ mTOR信号传导的药理学阻滞作用取消了原代B细胞淋巴瘤共培养中的促癌作用。因此，C /EBPβ在DC成熟和免疫刺激功能中起着独特的作用，并成为促进淋巴瘤发生的肿瘤微环境的关键因素。