CD206+ M2-Like Macrophages Are Essential for Successful Implantation.
CD206+ M2-Like Macrophages Are Essential for Successful Implantation.
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DOI：
10.3389/fimmu.2020.557184
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发表时间：
2020
影响因子：
7.3
通讯作者：
Saito S
中科院分区：
文献类型：
--
作者：
Ono Y;Yoshino O;Hiraoka T;Sato E;Fukui Y;Ushijima A;Nawaz A;Hirota Y;Wada S;Tobe K;Nakashima A;Osuga Y;Saito S
巨噬细胞（MΦs）在植入过程中起重要作用。据报道，CD11b-白喉毒素受体（DTR）小鼠中CD11b+ pan-MΦs的耗竭会导致黄体中黄体酮产生减少而导致着床失败。然而，在M1和M2中，对着床重要的MΦs类型尚不清楚。在本研究中，我们研究了M2 MΦ在CD206-DTR小鼠着床中的作用。为了消耗M2-MΦ，雌性CD206-DTR C57/BL6小鼠在植入前注射DT。这些M2-MΦ耗尽小鼠（M2(-)）与Balb/C小鼠自然交配。将注射DT的雌性C57/BL6野生型（WT）小鼠与雄性Balb/C小鼠交配作为对照组。测定着床部位数和着床时血浆黄体酮水平。应用定量pcr和免疫组化技术检测子宫组织中植入相关分子的表达。对38例着床失败患者在着床窗期子宫内膜mRNA表达进行了检测。在WT小鼠中，CD206+ m2样MΦs在着床期积聚于子宫内膜，在胚胎期(E) 4.5。M2（-）组植入数显著低于对照组（p < 0.001, 7.8±0.8 vs. 0.2±0.4），但血浆孕酮水平无明显变化。白血病抑制因子（LIF）和CD206 mRNA表达量显著降低（p < 0.01）， TNFα表达量显著升高（p < 0.05）。在M2（-）中，Ki-67+上皮细胞的数量在着床前明显高于对照组。子宫成纤维细胞生长因子（FGF）18 mRNA显著上调（P < 0.05）， M2（-）子宫内膜上皮细胞FGF18蛋白表达增强，证实了上皮细胞增殖加速。M2（-）在mRNA和蛋白水平上上调子宫Wnt/β-catenin信号。与妊娠组相比，未妊娠组子宫内膜组织中m2样蛋白MΦ / pan MΦ、CD206/CD68的比例显著降低（p < 0.05）， TNFα mRNA表达显著升高（p < 0.05）。CD206+ m2样MΦs可能通过Wnt/β-catenin信号传导调节子宫内膜增殖，对胚胎着床至关重要。
Macrophages (MΦs) play important roles in implantation. Depletion of CD11b+ pan-MΦs in CD11b-diphtheria-toxin-receptor (DTR) mice is reported to cause implantation failure due to decreased progesterone production in the corpus luteum. However, of the M1 and M2, the type of MΦs that is important for implantation is unknown. In this study, we investigated the role of M2 MΦ in implantation using CD206-DTR mice. To deplete M2-MΦ, female CD206-DTR C57/BL6 mice were injected with DT before implantation. These M2-MΦ depleted mice (M2(-)) were naturally mated with Balb/C mice. As the control group, female C57/BL6 wild type (WT) mice injected with DT were mated with male Balb/C mice. The number of implantation sites and plasma progesterone levels at implantation were examined. Implantation-related molecule expression was determined using quantitative-PCR and immunohistochemistry of uterine tissues. The mRNA expression in the endometrial tissues of 38 patients with implantation failure was examined during the implantation window. In WT mice, CD206+M2-like MΦs accumulated in the endometrium at the implantation period, on embryonic (E) 4.5. In M2(-), the implantation number was significantly lower than that in control (p < 0.001, 7.8 ± 0.8 vs. 0.2 ± 0.4), although the plasma progesterone levels were not changed. Leukemia inhibitory factor (LIF) and CD206 mRNA expression was significantly reduced (p < 0.01), whereas the levels of TNFα were increased on E4.5 (p < 0.05). In M2(-), the number of Ki-67+ epithelial cells was higher than that in control at the pre-implantation period. Accelerated epithelial cell proliferation was confirmed by significantly upregulated uterine fibroblast growth factor (FGF)18 mRNA (P < 0.05), and strong FGF18 protein expression in M2(-) endometrial epithelial cells. Further, M2(-) showed upregulated uterine Wnt/β-catenin signals at the mRNA and protein levels. In the non-pregnant group, the proportion of M2-like MΦ to pan MΦ, CD206/CD68, was significantly reduced (p < 0.05) and the TNFα mRNA expression was significantly increased (p < 0.05) in the endometrial tissues compared to those in the pregnant group. CD206+ M2-like MΦs may be essential for embryo implantation through the regulation of endometrial proliferation via Wnt/β-catenin signaling.
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影响因子：
82.9
作者：
Cha J;Sun X;Dey SK
通讯作者：
Dey SK
影响因子：
--
作者：
Douglas NC;Zimmermann RC;Tan QK;Sullivan-Pyke CS;Sauer MV;Kitajewski JK;Shawber CJ
通讯作者：
Shawber CJ
影响因子：
--
作者：
Sun, Xiaofei;Bartos, Amanda;Dey, Sudhansu K.
通讯作者：
Dey, Sudhansu K.
影响因子：
4.4
作者：
Svensson, Judit;Jenmalm, Maria C.;Ernerudh, Jan
通讯作者：
Ernerudh, Jan
影响因子：
4.6
作者：
Ono Y;Nagai M;Yoshino O;Koga K;Nawaz A;Hatta H;Nishizono H;Izumi G;Nakashima A;Imura J;Tobe K;Fujii T;Osuga Y;Saito S
通讯作者：
Saito S