Recruited macrophages that colonize the post-inflammatory peritoneal niche convert into functionally divergent resident cells.
Recruited macrophages that colonize the post-inflammatory peritoneal niche convert into functionally divergent resident cells.
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DOI：
10.1038/s41467-021-21778-0
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发表时间：
2021-03-19
影响因子：
16.6
通讯作者：
Jenkins SJ
中科院分区：
文献类型：
--
作者：
Louwe PA;Badiola Gomez L;Webster H;Perona-Wright G;Bain CC;Forbes SJ;Jenkins SJ
炎症通常导致单核细胞衍生的巨噬细胞的募集。是什么调节了这些细胞的命运，以及它们在多大程度上可以承担常驻巨噬细胞的身份和功能尚不清楚。在这里，我们表明，在轻度炎症引起的巨噬细胞进入腹腔长期存在，但由于持久的居民巨噬细胞的存在，保留在一个不成熟的过渡分化状态。相比之下，严重的炎症导致驻留巨噬细胞的消融和延长的阶段，其中腔不能维持驻留表型，但最终引发的细胞获得成熟的驻留身份。这些巨噬细胞还具有转录和功能上不同的特征，这些特征是由炎症驱动的腹膜腔微环境改变引起的，并且在较小程度上是起源和驻留时间的影响。因此，而不是预定的，炎症引起的腹腔巨噬细胞的命运似乎是由环境调节。腹膜腔是一个复杂的骨髓小生境，含有对炎症信号有反应的常驻巨噬细胞和浸润细胞的混合群体。在这里，作者追踪了这些浸润性巨噬细胞的命运，它们转化为驻留细胞以及随着时间的推移局部炎症状态如何改变。
Inflammation generally leads to recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident macrophages is unclear. Here, we show that macrophages elicited into the peritoneal cavity during mild inflammation persist long-term but are retained in an immature transitory state of differentiation due to the presence of enduring resident macrophages. By contrast, severe inflammation results in ablation of resident macrophages and a protracted phase wherein the cavity is incapable of sustaining a resident phenotype, yet ultimately elicited cells acquire a mature resident identity. These macrophages also have transcriptionally and functionally divergent features that result from inflammation-driven alterations to the peritoneal cavity micro-environment and, to a lesser extent, effects of origin and time-of-residency. Hence, rather than being predetermined, the fate of inflammation-elicited peritoneal macrophages seems to be regulated by the environment. The peritoneal cavity is a complicated myeloid niche containing a mixed population of resident macrophages and infiltrating cells that are responsive to inflammatory cues. Here the authors trace the fate of these infiltrating macrophages, their conversion to resident cells and how this is altered by the local inflammatory state over time.
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