Dysfunction of CCR1(+) decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss.
Dysfunction of CCR1(+) decidual macrophages is a potential risk factor in the occurrence of unexplained recurrent pregnancy loss.
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CCR1蜕膜巨噬细胞功能障碍是不明原因复发性流产发生的潜在危险因素
DOI：
10.3389/fimmu.2022.1045532
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发表时间：
2022
影响因子：
7.3
通讯作者：
Du, Meirong
中科院分区：
文献类型：
--
作者：
Sang, Yifei;Li, Yanhong;Xu, Ling;Chen, Jiajia;Li, Dajin;Du, Meirong
关键词：
复发性妊娠丢失（RPL）困扰着全世界1-3%的育龄妇女。免疫因素占不明原因RPL （URPL）病例的60%以上；然而，其潜在机制尚不清楚。在这里，利用单细胞测序数据和临床样本的功能实验，我们发现了一种独特的CCR1+蜕膜巨噬细胞（dMφ）群体，它们在正常早孕的蜕膜中优先富集，但在URPL患者中却大幅减少。特定的基因特征赋予CCR1+ dMφ免疫抑制和迁移调节特性，这些特性在URPL中减弱。此外，CCR1+ dMφ通过激活ERK1/2信号通路，促进上皮-间质转化（EMT），促进滋养细胞迁移和侵袭。蜕质细胞（DSC）衍生的CCL8是CCR1+ dMφ的关键调节因子，因为CCL8募集了外周CCR1+单核细胞，诱导了CCR1+ dMφ样表型，并增强了CCR1+ dMφ对滋养细胞的调节。在URPL患者中，DSCs中CCL8表达降低，滋养细胞EMT缺陷。我们的研究结果表明，CCR1+ dMφ在母胎界面的免疫耐受和滋养细胞功能中起重要作用。此外，CCR1+ dMφ的数量减少和功能失调导致URPL。总之，我们对母胎界面CCR1+ dMφ、滋养细胞和dsc之间的串扰以及URPL的巨噬细胞靶向干预提供了深入的了解。
Recurrent pregnancy loss (RPL) puzzles 1–3% of women of childbearing age worldwide. Immunological factors account for more than 60% of cases of unexplained RPL (URPL); however, the underlying mechanism remains unclear. Here, using single-cell sequencing data and functional experiments with clinical samples, we identified a distinct population of CCR1+ decidual macrophages (dMφ) that were preferentially enriched in the decidua from normal early pregnancies but were substantially decreased in patients with URPL. Specific gene signatures endowed CCR1+ dMφ with immunosuppressive and migration-regulatory properties, which were attenuated in URPL. Additionally, CCR1+ dMφ promoted epithelial-to-mesenchymal transition (EMT) to promote trophoblast migration and invasion by activating the ERK1/2 signaling pathway. Decidual stromal cell (DSC)-derived CCL8 was the key regulator of CCR1+ dMφ as CCL8 recruited peripheral CCR1+ monocytes, induced a CCR1+ dMφ-like phenotype, and reinforced the CCR1+ dMφ-exerted modulation of trophoblasts. In patients with URPL, CCL8 expression in DSCs was decreased and trophoblast EMT was defective. Our findings revealed that CCR1+ dMφ play an important role in immune tolerance and trophoblast functions at the maternal–fetal interface. Additionally, decreased quantity and dysregulated function of CCR1+ dMφ result in URPL. In conclusion, we provide insights into the crosstalk between CCR1+ dMφ, trophoblasts, and DSCs at the maternal–fetal interface and macrophage-targeted interventions of URPL.
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影响因子：
12.8
作者：
Eum HH;Kwon M;Ryu D;Jo A;Chung W;Kim N;Hong Y;Son DS;Kim ST;Lee J;Lee HO;Park WY
通讯作者：
Park WY
影响因子：
6.1
作者：
Helige, C.;Ahammer, H.;Sedlmayr, P.
通讯作者：
Sedlmayr, P.
影响因子：
5.6
作者：
Korbecki J;Kojder K;Simińska D;Bohatyrewicz R;Gutowska I;Chlubek D;Baranowska-Bosiacka I
通讯作者：
Baranowska-Bosiacka I
M1巨噬细胞衍生的细胞外囊泡传递miR-146a-5p和miR-146b-5p，通过靶向TRAF6抑制复发性流产中的滋养层细胞迁移和侵袭
影响因子：
12.4
作者：
Ding J;Zhang Y;Cai X;Zhang Y;Yan S;Wang J;Zhang S;Yin T;Yang C;Yang J
通讯作者：
Yang J
影响因子：
5.8
作者：
Farmaki, Elena;Kaza, Vimala;Kiaris, Hippokratis
通讯作者：
Kiaris, Hippokratis