Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
Immunity. 2017 Aug 15;47(2):349-362.e5. doi: 10.1016/j.immuni.2017.07.019. Epub 2017 Aug 8.
In lymph nodes (LNs), dendritic cells (DCs) are thought to dispose of apoptotic cells, a function pertaining to macrophages in other tissues. We found that a population of CX3CR1 MERTK cells located in the T cell zone of LNs, previously identified as DCs, are efferocytic macrophages. Lineage-tracing experiments and shield chimeras indicated that these T zone macrophages (TZM) are long-lived macrophages seeded in utero and slowly replaced by blood monocytes after birth. Imaging the LNs of mice in which TZM and DCs express different fluorescent proteins revealed that TZM-and not DCs-act as the only professional scavengers, clearing apoptotic cells in the LN T cell zone in a CX3CR1-dependent manner. Furthermore, similar to other macrophages, TZM appear inefficient in priming CD4 T cells. Thus, efferocytosis and T cell activation in the LN are uncoupled processes designated to macrophages and DCs, respectively, with implications to the maintenance of immune homeostasis.
在淋巴结 (LNs) 中,树突状细胞 (DCs) 被认为可以处理凋亡细胞,这一功能在其他组织中属于巨噬细胞。我们发现,位于 LNs 的 T 细胞区的一群 CX3CR1 MERTK 细胞,以前被鉴定为 DCs,实际上是具有吞噬作用的巨噬细胞。谱系追踪实验和屏蔽嵌合体表明,这些 T 区巨噬细胞(TZM)是在子宫内播下的长寿巨噬细胞,出生后由血液单核细胞缓慢替代。对表达不同荧光蛋白的 TZM 和 DC 的 LNs 进行成像显示,TZM(而非 DC)是唯一的专业清道夫,以 CX3CR1 依赖性方式清除 LN T 细胞区的凋亡细胞。此外,与其他巨噬细胞类似,TZM 在激活 CD4 T 细胞方面似乎效率不高。因此,LN 中的吞噬作用和 T 细胞激活是两个相互分离的过程,分别由巨噬细胞和 DC 负责,这对维持免疫稳态具有重要意义。