Diversification of human plasmacytoid predendritic cells in response to a single stimulus
Diversification of human plasmacytoid predendritic cells in response to a single stimulus
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DOI：
10.1038/s41590-017-0012-z
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发表时间：
2018-01-01
影响因子：
30.5
通讯作者：
Soumelis, Vassili
中科院分区：
文献类型：
--
作者：
Alculumbre, Solana G.;Saint-Andre, Violaine;Soumelis, Vassili
先天免疫细胞通过称为环境可塑性的过程来调节微生物和炎症刺激，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，激活人浆细胞样前树突状细胞（pDC）与一个单一的微生物或细胞因子刺激触发细胞分化成三个稳定的亚群（P1-P3）。P1-pDCs（PD-L1（+）CD 80（-））显示浆细胞样形态和I型干扰素产生的特化。P3-pDCs（PD-L1-CD 80（+））具有树突状形态和适应性免疫功能。P2-pDCs（PD-L1（+）CD 80（+））显示先天性和适应性功能。每个亚群都表达了一个特定的编码和长非编码RNA签名，并在二次刺激后保持稳定。在狼疮或银屑病患者的样品中检测到P1-pDC。pDC多样化独立于稳态pDC内的细胞分裂或预先存在的异质性，但受TNF自分泌和/或旁分泌通信回路控制。我们的发现揭示了先天免疫细胞多样性和劳动分工的新机制。
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.