Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH, USA.
Department of Pediatrics, National Jewish Health , Denver, CO, USA.
J Exp Med. 2023 Jun 5;220(6). doi: 10.1084/jem.20222129. Epub 2023 Mar 22.
Dendritic cells (DCs) and monocytes capture, transport, and present antigen to cognate T cells in the draining lymph nodes (LNs) in a CCR7-dependent manner. Since only migratory DCs express this chemokine receptor, it is unclear how monocytes reach the LN. In steady-state and following inhalation of several PAMPs, scRNA-seq identified LN mononuclear phagocytes as monocytes, resident, or migratory type 1 and type 2 conventional (c)DCs, despite the downregulation of Xcr1, Clec9a, H2-Ab1, Sirpa, and Clec10a transcripts on migratory cDCs. Migratory cDCs, however, upregulated Ccr7, Ccl17, Ccl22, and Ccl5. Migratory monocytes expressed Ccr5, a high-affinity receptor for Ccl5. Using two tracking methods, we observed that both CD88hiCD26lomonocytes and CD88-CD26hi cDCs captured inhaled antigens in the lung and migrated to LNs. Antigen exposure in mixed-chimeric Ccl5-, Ccr2-, Ccr5-, Ccr7-, and Batf3-deficient mice demonstrated that while antigen-bearing DCs use CCR7 to reach the LN, monocytes use CCR5 to follow CCL5-secreting migratory cDCs into the LN, where they regulate DC-mediated immunity.
树突状细胞 (DCs) 和单核细胞以 CCR7 依赖的方式捕获、转运和呈递抗原给引流淋巴结 (LNs) 中的同源 T 细胞。由于只有迁移的 DCs 表达这种趋化因子受体，因此尚不清楚单核细胞如何到达 LN。在稳态和吸入几种 PAMPs 后，scRNA-seq 将 LN 单核吞噬细胞鉴定为单核细胞、驻留或迁移的 1 型和 2 型常规 (c)DCs，尽管迁移的 cDCs 上的 Xcr1、Clec9a、H2-Ab1、Sirpa 和 Clec10a 转录本下调。然而，迁移的 cDCs 上调了 Ccr7、Ccl17、Ccl22 和 Ccl5。迁移的单核细胞表达 Ccr5，这是 Ccl5 的高亲和力受体。使用两种跟踪方法，我们观察到 CD88hiCD26lomonocytes 和 CD88-CD26hi cDCs 都在肺部捕获吸入的抗原并迁移到 LNs。在混合嵌合 Ccl5-、Ccr2-、Ccr5-、Ccr7- 和 Batf3 缺陷小鼠中的抗原暴露表明，虽然携带抗原的 DCs 使用 CCR7 到达 LN，但单核细胞使用 CCR5 跟随分泌 CCL5 的迁移 cDC 进入 LN，在那里它们调节 DC 介导的免疫。
