Myeloid-derived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells
Myeloid-derived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells
复制标题
骨髓源性抑制细胞耗竭可能通过上调蜕膜自然杀伤细胞的细胞毒性导致流产
DOI：
10.1111/aji.13099
复制
发表时间：
2019-04-01
影响因子：
3.6
通讯作者：
Lin, Yi
中科院分区：
文献类型：
--
作者：
Ren, Jiabin;Zeng, Weihong;Lin, Yi
问题
母体免疫系统对半同种异体胎儿的耐受对成功妊娠至关重要。研究表明，髓源性抑制细胞（MDSCs）在维持母胎耐受中起重要作用。然而，其机制仍知之甚少。
方法
采用流式细胞术评估同种异体正常妊娠小鼠模型在不同妊娠期MDSCs的百分比。我们进一步评估了自然流产小鼠模型中MDSCs及其亚型（粒细胞型MDSCs[GR - MDSCs]和单核细胞型MDSCs[MO - MDSCs]）的百分比。还评估了MDSCs中免疫抑制分子精氨酸酶 - 1（ARG - 1）、诱导型一氧化氮合酶（iNOS）、白细胞介素 - 10（IL - 10）和转化生长因子 - β（TGF - β）的水平。通过抗Gr - 1注射清除MDSCs，并计算吸收率。评估蜕膜自然杀伤（NK）细胞的细胞毒性，以及调节性NK（NKreg）细胞和调节性T淋巴细胞（Tregs）的百分比。
结果
髓源性抑制细胞在妊娠期间呈时间依赖性积累。然而，与对照小鼠相比，自然流产小鼠中MDSCs的百分比降低。此外，MDSCs中ARG - 1、iNOS、IL - 10和TGF - β的水平有差异地降低。最后，MDSCs的清除与吸收率增加以及子宫组织中NKreg和Treg细胞的比例相关；同时，通过增加穿孔素、颗粒酶B和自然杀伤细胞群2D激活受体（NKG2D）的水平，蜕膜NK细胞的细胞毒性上调。
结论
MDSCs的清除可能导致妊娠丢失，同时上调蜕膜NK细胞的细胞毒性并增加NKreg和Treg细胞数量。
Problem Maternal immune system tolerance to the semiallogeneic fetus is critical for a successful pregnancy. Studies have shown that myeloid-derived suppressor cells (MDSCs) play an important role in maintaining feto-maternal tolerance. However, the mechanisms remain poorly understood. Methods Flow cytometry was used to evaluate the percentage of MDSCs in an allogeneic-normal-pregnant mouse model during different periods of gestation. We further assessed the percentage of MDSCs and their subtypes (granulocytic MDSCs [GR-MDSCs] and monocytic MDSCs [MO-MDSCs]) in a spontaneous abortion mouse model. The levels of the immunosuppressive molecules ARG-1, iNOS, IL-10, and TGF-beta in MDSCs were also evaluated. MDSCs were depleted by anti-Gr-1 injection, and the resorption rate was calculated. The cytotoxicity of decidual natural killer (NK) cells was evaluated, and the percentage of regulatory NK (NKreg) cells and regulatory T lymphocytes (Tregs) were evaluated. Results Myeloid-derived suppressor cells was accumulated in a time-dependent manner during pregnancy. However, the percentage of MDSCs was decreased in the spontaneous abortion mice compared with that in the control mice. In addition, the levels of ARG-1, iNOS, IL-10, and TGF-beta in MDSCs decreased differentially. Finally, depletion of MDSCs was associated with increased rates of resorption and the proportion of NKreg and Treg cells in uterine tissues; meanwhile, the cytotoxicity of decidual NK cells was upregulated by increasing the level of perforin, granzyme B, and natural killer group protein 2 D-activating NK receptor (NKG2D). Conclusion Depletion of MDSCs may cause pregnancy loss, while upregulating the cytotoxicity of decidual NK cells and increasing NKreg and Treg cell numbers.