The lifespan and kinetics of human dendritic cell subsets and their precursors in health and inflammation.

IF 12.6 1区医学 Q1 IMMUNOLOGY Journal of Experimental Medicine Pub Date : 2024-11-04 Epub Date: 2024-10-17 DOI:10.1084/jem.20220867

Ruth Lubin, Amit A Patel, Jonas Mackerodt, Yan Zhang, Rotem Gvili, Kevin Mulder, Charles-Antoine Dutertre, Parinaaz Jalali, James R W Glanville, Idit Hazan, Nikhila Sridharan, Gurion Rivkin, Ayse Akarca, Teresa Marafioti, Derek W Gilroy, Leonid Kandel, Alexander Mildner, Asaf Wilensky, Becca Asquith, Florent Ginhoux, Derek Macallan, Simon Yona

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Abstract

Dendritic cells (DC) are specialized mononuclear phagocytes that link innate and adaptive immunity. They comprise two principal subsets: plasmacytoid DC (pDC) and conventional DC (cDC). Understanding the generation, differentiation, and migration of cDC is critical for immune homeostasis. Through human in vivo deuterium-glucose labeling, we observed the rapid appearance of AXL+ Siglec6+ DC (ASDC) in the bloodstream. ASDC circulate for ∼2.16 days, while cDC1 and DC2 circulate for ∼1.32 and ∼2.20 days, respectively, upon release from the bone marrow. Interestingly, DC3, a cDC subset that shares several similarities with monocytes, exhibits a labeling profile closely resembling that of DC2. In a human in vivo model of cutaneous inflammation, ASDC were recruited to the inflammatory site, displaying a distinctive effector signature. Taken together, these results quantify the ephemeral circulating lifespan of human cDC and propose functions of cDC and their precursors that are rapidly recruited to sites of inflammation.

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人类树突状细胞亚群及其前体在健康和炎症中的寿命和动力学。

树突状细胞（DC）是连接先天性免疫和适应性免疫的特化单核吞噬细胞。它们由两个主要亚群组成：浆细胞DC（pDC）和传统DC（cDC）。了解 cDC 的生成、分化和迁移对免疫平衡至关重要。通过人体体内氘-葡萄糖标记，我们观察到 AXL+ Siglec6+ DC（ASDC）在血液中迅速出现。ASDC循环时间为2.16天，而cDC1和DC2从骨髓中释放出来后的循环时间分别为1.32天和2.20天。有趣的是，DC3 是一种与单核细胞有若干相似之处的 cDC 亚群，其标记特征与 DC2 非常相似。在人体体内皮肤炎症模型中，ASDC 被招募到炎症部位，显示出独特的效应特征。总之，这些结果量化了人类 cDC 的短暂循环寿命，并提出了快速被招募到炎症部位的 cDC 及其前体的功能。

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来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.