SEC5 is involved in M2 polarization of macrophages via the STAT6 pathway, and its dysfunction in decidual macrophages is associated with recurrent spontaneous abortion.
SEC5 is involved in M2 polarization of macrophages via the STAT6 pathway, and its dysfunction in decidual macrophages is associated with recurrent spontaneous abortion.
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SEC5通过STAT6途径参与巨噬细胞的M2极化，其在蜕膜巨噬细胞中的功能障碍与复发性自然流产相关。
DOI：
10.3389/fcell.2022.891748
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发表时间：
2022
影响因子：
5.5
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Yang, Long;Zhang, Xuan;Gu, Yan;Shi, Yan;Wang, Long-Bin;Shi, Jia-Xin;Zhen, Xing-Xing;Xin, Ya-Wei;Gu, Wen-Wen;Wang, Jian
蜕膜巨噬细胞（dMphis）在怀孕期间母胎界面微稳态的建立中发挥着关键作用。妊娠早期巨噬细胞极化受损与复发性自然流产 (RSA) 相关。在本研究中，发现 RSA 患者原发 dM 中 SEC5 表达水平显着降低，并且 SEC5 表达下调抑制 M2 极化和 STAT6 磷酸化，而 M 中 SEC5 过表达在体外促进 M2 极化和 STAT6 磷酸化。我们随后发现 SEC5 在 THP-1 衍生的 Mphis 中与 STAT6 相互作用。 Mφs M2 极化后，磷酸化 STAT6 (pSTAT6) 蛋白丰度明显增加，主要分布在细胞核中，且 SEC5 蛋白与 pSTAT6 共定位。此外，在 RSA 患者的 dMφs 中观察到 pSTAT6 表达水平显着降低。 Mφs 的 M2 极化在体外对人绒毛外滋养层细胞 (EVT) 的增殖和侵袭具有刺激作用，而 Mφs 中 SEC5 表达的下调可有效逆转这种效应。在 LPS 诱导的早期妊娠流产的小鼠模型中，子宫 SEC5 表达水平和母胎界面处的 M2-Mphis 数量显着降低。更有趣的是，杂合性 SEC5 缺陷（SEC5−/+）怀孕小鼠对 LPS 诱导的流产更为敏感。综上所述，这些数据表明 SEC5 通过与 STAT6 相互作用参与调节 MΦs 的 M2 极化，并且 SEC5 表达减少会抑制 dMΦs 的 M2 极化，并通过干扰 EVT 的身体活动和母胎界面的免疫耐受而导致早期妊娠流产。
Decidual macrophages (dMϕs) play critical roles in the establishment of microhomeostasis at the maternal-fetal interface during pregnancy. Impaired macrophage polarization during early pregnancy is associated with recurrent spontaneous abortion (RSA). In the present study, the SEC5 expression level was found to be significantly decreased in primary dMϕs of patients with RSA, and downregulation of SEC5 expression inhibited M2 polarization and STAT6 phosphorylation, whereas SEC5 overexpression in the Mϕs promoted M2 polarization and STAT6 phosphorylation in vitro. We subsequently found that SEC5 interacted with STAT6 in THP-1-derived Mϕs. The abundance of phosphorylated STAT6 (pSTAT6) protein was obviously increased, with a predominant distribution in the nucleus, after M2 polarization of Mϕs, and SEC5 protein was colocalized with pSTAT6. Moreover, a significantly reduced pSTAT6 expression level was observed in the dMϕs of patients with RSA. M2 polarization of Mϕs showed a stimulatory effect on the proliferation and invasion of human extravillous trophoblasts (EVTs) in vitro, and downregulation of SEC5 expression in Mϕs effectively reversed this effect. In a mouse model of LPS-induced early pregnancy loss, the uterine SEC5 expression level and the number of M2-Mϕs at the maternal-fetal interface were significantly reduced. More interestingly, heterozygous SEC5-deficient (SEC5−/+) pregnant mice were more sensitive to LPS-induced pregnancy loss. Taken together, these data indicate that SEC5 participates in the regulation of M2 polarization of Mϕs by interacting with STAT6 and that decreased SEC5 expression inhibits the M2 polarization of dMϕs and results in early pregnancy loss by interfering with the physical activities of EVTs and immunotolerance at the maternal-fetal interface.
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影响因子：
3.8
作者：
Gonzalez, I. M.;Ackerman, W. E.;Vandre, D. D.;Robinson, J. M.
通讯作者：
Robinson, J. M.
影响因子：
3.7
作者：
Aisemberg J;Vercelli CA;Bariani MV;Billi SC;Wolfson ML;Franchi AM
通讯作者：
Franchi AM
影响因子：
64.5
作者：
Chien, Yuchen;Kim, Sungchan;White, Michael A.
通讯作者：
White, Michael A.
DOI：
10.4049/jimmunol.1003153
发表时间：
2011-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Houser BL;Tilburgs T;Hill J;Nicotra ML;Strominger JL
通讯作者：
Strominger JL
DOI：
10.1084/jem.20132349
发表时间：
2014-10-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jia XM;Tang B;Zhu LL;Liu YH;Zhao XQ;Gorjestani S;Hsu YM;Yang L;Guan JH;Xu GT;Lin X
通讯作者：
Lin X