胎源性巨噬細(xì)胞在成年乳腺中占主導(dǎo)地位

中文摘要：

巨噬細(xì)胞具有多種功能，包括免疫調(diào)節(jié)、形態(tài)發(fā)生、組織穩(wěn)態(tài)和愈合反應(yīng)。目前的觀點(diǎn)認(rèn)為，乳腺巨噬細(xì)胞在青春期前期出生后出現(xiàn)，來源于骨髓衍生的單核細(xì)胞。在此，我們通過高維表型分析、細(xì)胞命運(yùn)追蹤實(shí)驗(yàn)、缺失特定巨噬細(xì)胞亞型的基因缺陷小鼠以及基于抗體的消耗策略，闡明了組織駐留乳腺巨噬細(xì)胞的起源。我們發(fā)現(xiàn)，組織駐留巨噬細(xì)胞在出生前便存在于乳腺中，而且卵黃囊來源和胎肝來源的巨噬細(xì)胞在成年乳腺中數(shù)量仍多于成人來源的巨噬細(xì)胞。此外，胎兒來源的乳腺巨噬細(xì)胞具有特征性表型，顯示出偏向?qū)Ч苤車脱苤車亩ㄎ?，并在清除功能上非常活躍。這些發(fā)現(xiàn)將胎兒來源的巨噬細(xì)胞確定為成年乳腺基質(zhì)中主要的白細(xì)胞類型，并揭示了乳腺巨噬細(xì)胞生物學(xué)此前未知的復(fù)雜性。

英文摘要：

Macrophages serve multiple functions including immune regulation, morphogenesis, tissue homeostasis and healing reactions. The current paradigm holds that mammary gland macrophages first arise postnatally during the prepubertal period from the bone marrow-derived monocytes. Here we delineate the origins of tissue-resident mammary gland macrophages using high-dimension phenotypic analyses, cell-fate mapping experiments, gene-deficient mice lacking selective macrophage subtypes, and antibody-based depletion strategies. We show that tissue-resident macrophages are found in mammary glands already before birth, and that the yolk sac-derived and fetal liver-derived macrophages outnumber the adult-derived macrophages in the mammary gland also in the adulthood. In addition, fetal-derived mammary gland macrophages have a characteristic phenotype, display preferential periductal and perivascular localization, and are highly active in scavenging. These findings identify fetal-derived macrophages as the predominant leukocyte type in the adult mammary gland stroma, and reveal previously unknown complexity of macrophage biology in the breast.

論文信息：

論文題目：Fetal-derived macrophages dominate in adult mammary glands

期刊名稱：Nature Communications

時(shí)間期卷：10, Article number: 281(2019)

在線時(shí)間：2019年1月17日

DOI： doi.org/10.1038/s41467-018-08065-1

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control liposomes

辦事處：Target Technology(靶點(diǎn)科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體聯(lián)合抗體清除外周和乳腺定居巨噬細(xì)胞 ，荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于Nature Communications：胎源性巨噬細(xì)胞在成年乳腺中占主導(dǎo)地位。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除乳腺巨噬細(xì)胞的材料和方法：

Macrophage depletion

To deplete YS-derived macrophages pregnant female mice were treated with a single injection of CSF-1R blocking antibody (clone AFS98, Bio X Cell) or rat IgG2a control antibody (clone 2A3, Bio X Cell). Three mg of the antibodies in sterile PBS were administered i.p. to pregnant females at E6.5, as described12,32. Mice were sacrificed at E17.5 or at postnatal age of 2 wk or 5 wk for flow cytometric analyses.

To deplete tissue-resident macrophages after birth, 2 wk old C57Bl/6N mice were cyclically treated with anti-CSF1 antibody and clodronate (Fig. 2b). To that end, three doses of CSF1 neutralizing antibody (Clone 5A1, BioXcell) or control IgG (clone HRPN, BioXcell) were given i.p. (0.5?mg on postnatal day 14, 0.25?mg on postnatal day 18 and 0.25?mg on postnatal day 22). On subsequent days, three doses of clodronate or control liposomes (Liposoma) 50?µl/injection on postnatal days 15, 19 and 23) were administered i.v. The mice were sacrificed 1 or 11 days after the final clodronate treatment. In control experiments using kidney, we saw a full recovery of a known bone marrow-derived CD11b+F4/80Int macrophage population, but not that of a known fetal-derived CD11bIntF4/80Hi macrophage population, verifying the robustness of the model.

材料和方法文獻(xiàn)截圖：