Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Immune Responses to Lipids Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Cell Rep. 2023 Aug 29;42(8):112881. doi: 10.1016/j.celrep.2023.112881. Epub 2023 Jul 30.
Conventional dendritic cells (cDCs) are found in most tissues and play a key role in initiation of immunity. cDCs require constant replenishment from progenitors called pre-cDCs that develop in the bone marrow (BM) and enter the blood circulation to seed all tissues. This process can be markedly accelerated in response to inflammation (emergency cDCpoiesis). Here, we identify two populations of BM pre-cDC marked by differential expression of CXCR4. We show that CXCR4 cells constitute the migratory pool of BM pre-cDCs, which exits the BM and can be rapidly mobilized during challenge. We further show that exit of CXCR4 pre-cDCs from BM at steady state is partially dependent on CCR2 and that CCR2 upregulation in response to type I IFN receptor signaling markedly increases efflux during infection with influenza A virus. Our results highlight a fine balance between retention and efflux chemokine cues that regulates steady-state and emergency cDCpoiesis.
常规树突状细胞 (cDCs) 存在于大多数组织中，在启动免疫中发挥关键作用。cDCs 需要不断从称为前体树突状细胞 (pre-cDCs) 的祖细胞中得到补充，这些祖细胞在骨髓 (BM) 中发育并进入血液循环，以播散到所有组织中。这种过程在炎症反应中可以显著加速（应急树突状细胞生成）。在这里，我们鉴定了两种 BM 前体树突状细胞亚群，它们通过 CXCR4 的差异表达来标记。我们表明，CXCR4 细胞构成了 BM 前体树突状细胞的迁移池，它们离开 BM 并可以在受到挑战时迅速动员。我们进一步表明，在稳态下，CXCR4 前体树突状细胞从 BM 中的退出部分依赖于 CCR2，并且对 I 型 IFN 受体信号的 CCR2 上调在感染甲型流感病毒时会显著增加流出。我们的结果突出了调节稳态和应急树突状细胞生成的保留和流出趋化因子信号之间的精细平衡。
