Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Roche, Basel, Switzerland.
Nat Immunol. 2023 Jul;24(7):1098-1109. doi: 10.1038/s41590-023-01530-0. Epub 2023 Jun 19.
Macrophages are involved in immune defense, organogenesis and tissue homeostasis. Macrophages contribute to the different phases of mammary gland remodeling during development, pregnancy and involution postlactation. Less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multiparameter flow cytometry and single-cell RNA sequencing, we identified a lactation-induced CD11cCX3CR1Dectin-1 macrophage population (liMac) that was distinct from the two resident F4/80 and F4/80 macrophage subsets present pregestationally. LiMacs were predominantly monocyte-derived and expanded by proliferation in situ concomitant with nursing. LiMacs developed independently of IL-34, but required CSF-1 signaling and were partly microbiota-dependent. Locally, they resided adjacent to the basal cells of the alveoli and extravasated into the milk. We found several macrophage subsets in human milk that resembled liMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.
巨噬细胞参与免疫防御、器官发生和组织稳态。巨噬细胞在乳腺发育、妊娠和哺乳期后退化的不同阶段都参与了乳腺重塑。关于哺乳期乳腺巨噬细胞的动态变化知之甚少。在这里，我们描述了小鼠哺乳期存在的一种巨噬细胞群体。通过多参数流式细胞术和单细胞 RNA 测序，我们鉴定出一种在哺乳期诱导的 CD11cCX3CR1Dectin-1 巨噬细胞群体（liMac），它与妊娠前存在的两种常驻 F4/80 和 F4/80 巨噬细胞亚群不同。LiMac 主要来源于单核细胞，并通过原位增殖而扩张，伴随着哺乳。LiMac 的发育不依赖于 IL-34，但需要 CSF-1 信号，并在一定程度上依赖于微生物群。在局部，它们位于肺泡的基底层旁边，并渗出到乳汁中。我们在人乳中发现了一些类似于 liMac 的巨噬细胞亚群。总的来说，这些发现揭示了在哺乳期乳腺和乳汁中独特的巨噬细胞的出现。
