Innate immune cells adjust to microbial and inflammatory stimuli through a process termed environmental plasticity, which links a given individual stimulus to a unique activated state. Here, we report that activation of human plasmacytoid predendritic cells (pDCs) with a single microbial or cytokine stimulus triggers cell diversification into three stable subpopulations (P1-P3). P1-pDCs (PD-L1⁺CD80^-) displayed a plasmacytoid morphology and specialization for type I interferon production. P3-pDCs (PD-L1^-CD80⁺) adopted a dendritic morphology and adaptive immune functions. P2-pDCs (PD-L1⁺CD80⁺) displayed both innate and adaptive functions. Each subpopulation expressed a specific coding- and long-noncoding-RNA signature and was stable after secondary stimulation. P1-pDCs were detected in samples from patients with lupus or psoriasis. pDC diversification was independent of cell divisions or preexisting heterogeneity within steady-state pDCs but was controlled by a TNF autocrine and/or paracrine communication loop. Our findings reveal a novel mechanism for diversity and division of labor in innate immune cells.

中文翻译：

---

人类浆细胞样树突状细胞对单一刺激的反应多样化。

先天性免疫细胞通过称为环境可塑性的过程适应微生物和炎性刺激，该过程将给定的个体刺激与独特的激活状态联系起来。在这里，我们报告说，具有单个微生物或细胞因子刺激的人类浆细胞样树突状细胞（pDCs）的激活会触发细胞多样化成三个稳定的亚群（P1-P3）。P1-的pDCs（PD-L1 ⁺ CD80 ^- ）显示的浆形态和专业化为I型干扰素的产生。P3-pDC（PD-L1 ^- CD80 ⁺）采用树突形态和适应性免疫功能。P2-pDC（PD-L1 ⁺ CD80 ⁺）同时显示了固有功能和自适应功能。每个亚群均表达特定的编码和长非编码RNA签名，并且在二次刺激后保持稳定。在狼疮或牛皮癣患者的样本中检测到P1-pDC。pDC的多样化与稳态pDC内的细胞分裂或先前存在的异质性无关，但受TNF自分泌和/或旁分泌通讯回路控制。我们的发现揭示了先天免疫细胞多样性和分工的新机制。