Key Points IRF4ΔDC mice control bacterial infections and tumors more efficiently than WT mice. Th1 responses are enhanced and Th2 responses are reduced in IRF4ΔDC mice. IRF4 drives immunoregulatory activities and RALDH2 expression in cDC2s. The lamina propria of the gastrointestinal tract and other mucosal surfaces of humans and mice host a network of mononuclear phagocytes that differ in their ontogeny, surface marker and transcription factor expression, and functional specialization. Conventional dendritic cells (DCs) in particular exist as two major subpopulations in both lymphoid and nonlymphoid organs that can be distinguished based on their surface marker and transcription factor expression. In this study, we show in various Th1- and/or Th17-polarized settings of acute and chronic bacterial infection and of tumor growth that the conditional ablation of Irf4 in CD11c+ DCs results in more efficient immune control of Helicobacter pylori, Mycobacterium bovis bacillus Calmette–Guérin, and Citrobacter rodentium and of tumor growth in a syngeneic tumor model. We attribute the phenotype of IRF4ΔDC mice to unrestricted Th1 responses and in particular to IFN-γ– and TNF-α–expressing CD4+ T cells. This activity of IRF4-expressing DCs is linked to a DC-specific immunoregulatory transcriptional program. In contrast, in Th2-polarized settings such as house dust mite–induced allergic airway inflammation, the lack of IRF4 expression in the DC compartment alleviates inflammation and goblet cell metaplasia. The combined data provide evidence for immunoregulatory properties of this versatile DC population in Th1-polarized infection settings.

中文翻译：

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IRF4 表达是慢性细菌感染和癌症环境中常规 2 型树突细胞的免疫调节活性所必需的

关键点 IRF4ΔDC 小鼠比 WT 小鼠更有效地控制细菌感染和肿瘤。在 IRF4ΔDC 小鼠中，Th1 反应增强而 Th2 反应降低。IRF4 驱动 cDC2s 中的免疫调节活性和 RALDH2 表达。胃肠道的固有层和人类和小鼠的其他粘膜表面承载着一个单核吞噬细胞网络，这些吞噬细胞在个体发育、表面标记和转录因子表达以及功能特化方面有所不同。传统的树突状细胞 (DC) 尤其作为淋巴和非淋巴器官中的两个主要亚群存在，可以根据它们的表面标记和转录因子表达进行区分。在这项研究中，我们在急性和慢性细菌感染和肿瘤生长的各种 Th1 和/或 Th17 极化环境中表明，CD11c+ DC 中 Irf4 的有条件消融导致对幽门螺杆菌、牛分枝杆菌 Calmette-Guérin 的更有效免疫控制，以及Citrobacter Rodentium 和同源肿瘤模型中的肿瘤生长。我们将 IRF4ΔDC 小鼠的表型归因于不受限制的 Th1 反应，特别是表达 IFN-γ 和 TNF-α 的 CD4+ T 细胞。表达 IRF4 的 DC 的这种活性与 DC 特异性免疫调节转录程序有关。相比之下，在屋尘螨引起的过敏性气道炎症等 Th2 极化环境中，DC 室中 IRF4 表达的缺乏减轻了炎症和杯状细胞化生。