Laboratory of Immunophysiology, GIGA Institute, Liège University, Avenue de l'Hôpital 11, B34, 4000, Liège, Belgium.
Laboratory of Cellular and Molecular Immunology, GIGA Institute, Liège University, Avenue de l'Hôpital 11, B34, 4000, Liège, Belgium.
Nat Commun. 2019 Sep 3;10(1):3964. doi: 10.1038/s41467-019-11843-0.
Resident tissue macrophages (RTM) can fulfill various tasks during development, homeostasis, inflammation and repair. In the lung, non-alveolar RTM, called interstitial macrophages (IM), importantly contribute to tissue homeostasis but remain little characterized. Here we show, using single-cell RNA-sequencing (scRNA-seq), two phenotypically distinct subpopulations of long-lived monocyte-derived IM, i.e. CD206 and CD206IM, as well as a discrete population of extravasating CD64CD16.2 monocytes. CD206 IM are peribronchial self-maintaining RTM that constitutively produce high levels of chemokines and immunosuppressive cytokines. Conversely, CD206IM preferentially populate the alveolar interstitium and exhibit features of antigen-presenting cells. In addition, our data support that CD64CD16.2 monocytes arise from intravascular Ly-6C patrolling monocytes that enter the tissue at steady-state to become putative precursors of CD206IM. This study expands our knowledge about the complexity of lung IM and reveals an ontogenic pathway for one IM subset, an important step for elaborating future macrophage-targeted therapies.
驻留组织巨噬细胞（RTM）在发育、稳态、炎症和修复过程中可以完成各种任务。在肺部，非肺泡 RTM，称为间质巨噬细胞（IM），对组织稳态有重要贡献，但特征仍知之甚少。在这里，我们使用单细胞 RNA 测序（scRNA-seq）显示了两种表型上不同的长寿命单核细胞衍生的 IM 亚群，即 CD206 和 CD206IM，以及离散的血管外渗 CD64CD16.2 单核细胞群。CD206 IM 是位于支气管周围的自我维持的 RTM，它们持续产生高水平的趋化因子和免疫抑制细胞因子。相反，CD206IM 优先定殖于肺泡间质，并表现出抗原呈递细胞的特征。此外，我们的数据支持 CD64CD16.2 单核细胞来源于血管内 Ly-6C 巡逻单核细胞，它们在稳态时进入组织，成为 CD206IM 的潜在前体。这项研究扩展了我们对肺 IM 复杂性的认识，并揭示了一种 IM 亚群的发生途径，这是制定未来巨噬细胞靶向治疗的重要步骤。
