MNSFβ Regulates TNFα Production by Interacting with RC3H1 in Human Macrophages, and Dysfunction of MNSFβ in Decidual Macrophages Is Associated With Recurrent Pregnancy Loss.
MNSFβ Regulates TNFα Production by Interacting with RC3H1 in Human Macrophages, and Dysfunction of MNSFβ in Decidual Macrophages Is Associated With Recurrent Pregnancy Loss.
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MNSFβ 通过与人类巨噬细胞中的 RC3H1 相互作用来调节 TNFα 的产生，蜕膜巨噬细胞中 MNSFβ 的功能障碍与复发性妊娠丢失有关
DOI：
10.3389/fimmu.2021.691908
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Zhen XX;Yang L;Gu Y;Yang Q;Gu WW;He YP;Wang YL;Wang J
蜕膜巨噬细胞（dM巨噬细胞）是母胎界面的第二大白细胞群体，并且在维持妊娠中起关键作用。我们前期的研究表明单克隆非特异性抑制因子β（MNSFβ）在胚胎植入和妊娠成功中起着积极的作用。MNSFβ是一种广泛表达的泛素样蛋白，也具有免疫调节潜力，但其在人类dM β中的功能仍不清楚。在这里，我们观察到，与正常孕妇（对照dM β）相比，复发性流产患者（RPL dM β）的dM β中CD 11 chigh（CD 11 cHI）dM β的比例显著增加。与对照dM β相比，RPL dM β产生的MNSFβ和TNFα也显著增加。RPL dM β条件培养液对人滋养层细胞HTR 8/SVneo的侵袭力有抑制作用，这种作用可被TNFα中和抗体部分逆转。生物信息学分析表明，MNSFβ与TNFα转录抑制因子RC 3 H1可能存在相互作用。用从人单核细胞系Thp 1分化的人M β（Thp 1衍生的M β）进行的免疫沉淀实验证明了MNSFβ与RC 3 H1的结合。在Thp 1来源的M细胞中特异性敲低MNSFβ导致TNFα产生显著减少，这可以通过抑制RC 3 H1表达来逆转。有趣的是，在RPL dM中观察到RC 3 H1的蛋白水平显着下降。总之，我们的研究结果表明，异常增加的MNSFβ表达dM胎儿可能通过其与RC 3 H1的相互作用促进TNFα的产生，这些现象可能导致母胎界面的免疫平衡破坏，从而导致妊娠丢失。
Decidual macrophages (dMϕ) are the second largest population of leukocytes at the maternal–fetal interface and play critical roles in maintaining pregnancy. Our previous studies demonstrated the active involvement of monoclonal nonspecific suppressor factor-β (MNSFβ) in embryonic implantation and pregnancy success. MNSFβ is a ubiquitously expressed ubiquitin-like protein that also exhibits immune regulatory potential, but its function in human dMϕ remains unknown. Here, we observed that the proportion of CD11chigh (CD11cHI) dMϕ was significantly increased in dMϕ derived from patients with recurrent pregnancy loss (RPL dMϕ) compared to those derived from normal pregnant women (Control dMϕ). The production of MNSFβ and TNFα by RPL dMϕ was also significantly increased compared to that by Control dMϕ. Conditioned medium from RPL dMϕ exerted an inhibitory effect on the invasiveness of human trophoblastic HTR8/SVneo cells, and this effect could be partially reversed by a neutralizing antibody against TNFα. Bioinformatics analysis indicated a potential interaction between MNSFβ and RC3H1, a suppressor of TNFα transcription. Immunoprecipitation experiments with human Mϕ differentiated from the human monocyte cell line Thp1 (Thp1-derived Mϕ) proved the binding of MNSFβ to RC3H1. Specific knockdown of MNSFβ in Thp1-derived Mϕ led to a marked decrease in TNFα production, which could be reversed by inhibiting RC3H1 expression. Interestingly, a significant decrease in the protein level of RC3H1 was observed in RPL dMϕ. Together, our findings indicate that aberrantly increased MNSFβ expression in dMϕ may promote TNFα production via its interaction with RC3H1, and these phenomena could result in the disruption of the immune balance at the maternal–fetal interface and thus pregnancy loss.
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影响因子：
3.5
作者：
NAKAMURA, M;XAVIER, RM;TANIGAWA, Y
通讯作者：
TANIGAWA, Y
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
影响因子：
7.7
作者：
Pique-Regi, Roger;Romero, Roberto;Gomez-Lopez, Nardhy
通讯作者：
Gomez-Lopez, Nardhy
M2巨噬细胞源性G-CSF通过激活PI3K/Akt/Erk1/2通路促进滋养层细胞EMT、侵袭和迁移介导正常妊娠
影响因子：
5.3
作者：
Ding J;Yang C;Zhang Y;Wang J;Zhang S;Guo D;Yin T;Yang J
通讯作者：
Yang J
DOI：
10.1016/j.bbrc.2010.09.045
发表时间：
2010-10-15
影响因子：
3.1
作者：
Nakamura, Morihiko;Watanabe, Natsuko
通讯作者：
Watanabe, Natsuko