Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Immunology Program, Stanford University School of Medicine, Stanford, CA, USA.
Nat Immunol. 2023 Aug;24(8):1265-1280. doi: 10.1038/s41590-023-01545-7. Epub 2023 Jul 6.
High-dimensional approaches have revealed heterogeneity amongst dendritic cells (DCs), including a population of transitional DCs (tDCs) in mice and humans. However, the origin and relationship of tDCs to other DC subsets has been unclear. Here we show that tDCs are distinct from other well-characterized DCs and conventional DC precursors (pre-cDCs). We demonstrate that tDCs originate from bone marrow progenitors shared with plasmacytoid DCs (pDCs). In the periphery, tDCs contribute to the pool of ESAM type 2 DCs (DC2s), and these DC2s have pDC-related developmental features. Different from pre-cDCs, tDCs have less turnover, capture antigen, respond to stimuli and activate antigen-specific naïve T cells, all characteristics of differentiated DCs. Different from pDCs, viral sensing by tDCs results in IL-1β secretion and fatal immune pathology in a murine coronavirus model. Our findings suggest that tDCs are a distinct pDC-related subset with a DC2 differentiation potential and unique proinflammatory function during viral infections.
高维方法揭示了树突状细胞（DCs）的异质性，包括小鼠和人类中的过渡性 DC（tDC）群体。然而，tDC 与其他 DC 亚群的起源和关系尚不清楚。在这里，我们表明 tDC 与其他特征明确的 DC 和传统的 DC 前体（pre-cDC）不同。我们证明 tDC 起源于与浆细胞样 DC（pDC）共享的骨髓祖细胞。在外周，tDC 有助于 ESAM 类型 2 DC（DC2）池的形成，并且这些 DC2 具有与 pDC 相关的发育特征。与 pre-cDC 不同，tDC 的周转率较低，捕获抗原，对刺激物作出反应并激活抗原特异性初始 T 细胞，所有这些都是分化 DC 的特征。与 pDC 不同，tDC 对病毒的感应会导致 IL-1β 分泌，并在小鼠冠状病毒模型中导致致命的免疫病理。我们的研究结果表明，tDC 是一种独特的 pDC 相关亚群，具有 DC2 分化潜能和在病毒感染期间的独特促炎功能。
