髓源性抑制细胞对正常妊娠及病理妊娠的影响

doi:10.12280/gjfckx.20250785

摘要/Abstract

摘要：

髓源性抑制细胞（myeloid-derived suppressor cell，MDSC）是一类具有免疫特性的髓系祖细胞，此类细胞不仅具有免疫抑制性及炎症促进作用，同时对正常妊娠的建立和病理妊娠的发展至关重要。其中，MDSC的增殖促进病原体感染同时也加速肿瘤进展。除此之外，MDSC对于建立母胎免疫耐受保证母胎界面的稳定性不可或缺。然而，MDSC功能失衡或数量异常便会导致自然流产、子痫前期、胎儿生长受限、复发性流产，甚至早产和死胎等危及母儿安全相关的病理妊娠发生。因此，深入研究MDSC的基本特性及其在妊娠及妊娠相关疾病发生中的作用机制，有望在母胎医学的进一步探索和病理妊娠早期预防、早期诊断中提供重要的理论依据及诊治方向。

关键词: 髓源性抑制细胞, 免疫调节, 妊娠, 妊娠并发症, 先兆子痫, 胎儿生长迟缓

Abstract:

Myeloid-derived suppressor cells (MDSCs) are a type of myeloid progenitor cells with immune characteristics. These cells not only have immunosuppressive and inflammation-promoting effects, but also crucial for the establishment of normal pregnancy as well as the development of pathological pregnancy. Among them, the proliferation of MDSC promotes pathogen infection and accelerates tumor progression. Moreover, MDSC are indispensable for establishing maternal-fetal immune tolerance and ensuring the stability of the maternal-fetal interface. However, the imbalance of MDSC function or abnormal quantity can lead to pathological pregnancies that endanger the safety of the mother and the fetus, such as spontaneous abortion, preeclampsia, fetal growth restriction, recurrent miscarriage, and even preterm birth and stillbirth. Therefore, in-depth research on the basic characteristics of MDSC and their mechanism of action in pregnancy and pregnancy-related diseases is expected to provide important theoretical basis and diagnosis-treatment directions for the further exploration of maternal-fetal medicine and the early prevention and diagnosis of pathological pregnancy.

Key words: Myeloid-derived suppressor cells, Immunomodulation, Pregnancy, Pregnancy complications, Pre-eclampsia, Fetal growth retardation

王馨艺, 祝彩霞. 髓源性抑制细胞对正常妊娠及病理妊娠的影响[J]. 国际妇产科学杂志, 2025, 52(6): 649-653.

WANG Xin-yi, ZHU Cai-xia. Effects of Myeloid-Derived Suppressor Cells on Normal Pregnancy and Pathological Pregnancy[J]. Journal of International Obstetrics and Gynecology, 2025, 52(6): 649-653.

参考文献 38

[1]	Liu X, Wang G, Huang H, et al. Exploring maternal-fetal interface with in vitro placental and trophoblastic models[J]. Front Cell Dev Biol, 2023, 11:1279227. doi: 10.3389/fcell.2023.1279227.
[2]	Shah NK, Xu P, Shan Y, et al. MDSCs in pregnancy and pregnancy-related complications: an update[J]. Biol Reprod, 2023, 108(3):382-392. doi: 10.1093/biolre/ioac213.
[3]	He S, Zheng L, Qi C. Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy[J]. Mol Cancer, 2025, 24(1):5. doi: 10.1186/s12943-024-02208-3. pmid: 39780248
[4]	Gabrilovich DI, Bronte V, Chen SH, et al. The terminology issue for myeloid-derived suppressor cells[J]. Cancer Res, 2007, 67(1):425; author reply 426. doi: 10.1158/0008-5472.CAN-06-3037.
[5]	Lasser SA, Ozbay Kurt FG, Arkhypov I, et al. Myeloid-derived suppressor cells in cancer and cancer therapy[J]. Nat Rev Clin Oncol, 2024, 21(2):147-164. doi: 10.1038/s41571-023-00846-y. pmid: 38191922
[6]	Zhang MN, Yuan YL, Ao SH. Advances in the study of myeloid-derived suppressor cells in infectious lung diseases[J]. Front Immunol, 2023, 14:1125737. doi: 10.3389/fimmu.2023.1125737.
[7]	Grassi G, Notari S, Gili S, et al. Myeloid-Derived Suppressor Cells in COVID-19: The Paradox of Good[J]. Front Immunol, 2022, 13:842949. doi: 10.3389/fimmu.2022.842949.
[8]	Glover A, Zhang Z, Shannon-Lowe C. Deciphering the roles of myeloid derived suppressor cells in viral oncogenesis[J]. Front Immunol, 2023, 14:1161848. doi: 10.3389/fimmu.2023.1161848.
[9]	Yaseen MM, Abuharfeil NM, Darmani H. MDSC expansion during HIV infection: regulators, ART and immune reconstitution[J]. Genes Immun, 2024, 25(3):242-253. doi: 10.1038/s41435-024-00272-9. pmid: 38605259
[10]	Wu Y, Yi M, Niu M, et al. Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy[J]. Mol Cancer, 2022, 21(1):184. doi: 10.1186/s12943-022-01657-y. pmid: 36163047
[11]	Wang C, Zheng X, Zhang J, et al. CD300ld on neutrophils is required for tumour-driven immune suppression[J]. Nature, 2023, 621(7980):830-839. doi: 10.1038/s41586-023-06511-9.
[12]	Zhang R, Dong M, Tu J, et al. PMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway[J]. Signal Transduct Target Ther, 2023, 8(1):97. doi: 10.1038/s41392-023-01337-3.
[13]	de Toledo MA, de Lima J, Salomão R, et al. Characterizing a low-density neutrophil gene signature in acute and chronic infections and its impact on disease severity[J]. J Leukoc Biol, 2025, 117(4):qiaf027. doi: 10.1093/jleuko/qiaf027.
[14]	Carmona-Rivera C, Kaplan MJ. Low-density granulocytes in systemic autoimmunity and autoinflammation[J]. Immunol Rev, 2023, 314(1):313-325. doi: 10.1111/imr.13161.
[15]	Ning X, Wang WM, Jin HZ. Low-Density Granulocytes in Immune-Mediated Inflammatory Diseases[J]. J Immunol Res, 2022, 2022:1622160. doi: 10.1155/2022/1622160.
[16]	Wang P, Xu L, Bai M, et al. MDSCs are important osteoclast precursors primed by B cells in rheumatoid arthritis[J]. Eur J Immunol, 2024, 54(9):e2350823. doi: 10.1002/eji.202350823.
[17]	Henning S, Reimers T, Abdulahad W, et al. Low-density granulocytes and neutrophil extracellular trap formation are increased in incomplete systemic lupus erythematosus[J]. Rheumatology(Oxford), 2025, 64(3):1234-1242. doi: 10.1093/rheumatology/keae300.
[18]	Hu C, Zhen Y, Ma Z, et al. Polyamines from myeloid-derived suppressor cells promote Th17 polarization and disease progression[J]. Mol Ther, 2023, 31(2):569-584. doi: 10.1016/j.ymthe.2022.10.013.
[19]	Yang F, Zheng Q, Jin L. Dynamic Function and Composition Changes of Immune Cells During Normal and Pathological Pregnancy at the Maternal-Fetal Interface[J]. Front Immunol, 2019, 10:2317. doi: 10.3389/fimmu.2019.02317. pmid: 31681264
[20]	Pang B, Hu C, Li H, et al. Myeloidderived suppressor cells: Escorts at the maternal-fetal interface[J]. Front Immunol, 2023, 14:1080391. doi: 10.3389/fimmu.2023.1080391.
[21]	Aplin JD, Myers JE, Timms K, et al. Tracking placental development in health and disease[J]. Nat Rev Endocrinol, 2020, 16(9):479-494. doi: 10.1038/s41574-020-0372-6. pmid: 32601352
[22]	Köstlin N, Hofstädter K, Ostermeir AL, et al. Granulocytic Myeloid-Derived Suppressor Cells Accumulate in Human Placenta and Polarize toward a Th2 Phenotype[J]. J Immunol, 2016, 196(3):1132-1145. doi: 10.4049/jimmunol.1500340. pmid: 26712947
[23]	Köstlin-Gille N, Dietz S, Schwarz J, et al. HIF-1α-Deficiency in Myeloid Cells Leads to a Disturbed Accumulation of Myeloid Derived Suppressor Cells (MDSC) During Pregnancy and to an Increased Abortion Rate in Mice[J]. Front Immunol, 2019, 10:161. doi: 10.3389/fimmu.2019.00161. pmid: 30804946
[24]	Köstlin N, Kugel H, Spring B, et al. Granulocytic myeloid derived suppressor cells expand in human pregnancy and modulate T-cell responses[J]. Eur J Immunol, 2014, 44(9):2582-2591. doi: 10.1002/eji.201344200. pmid: 24894988
[25]	Hu C, Zhen Y, Pang B, et al. Myeloid-Derived Suppressor Cells Are Regulated by Estradiol and Are a Predictive Marker for IVF Outcome[J]. Front Endocrinol(Lausanne), 2019, 10:521. doi: 10.3389/fendo.2019.00521.
[26]	Köstlin N, Schoetensack C, Schwarz J, et al. Granulocytic Myeloid-Derived Suppressor Cells (GR-MDSC) in Breast Milk (BM); GR-MDSC Accumulate in Human BM and Modulate T-Cell and Monocyte Function[J]. Front Immunol, 2018, 9:1098. doi: 10.3389/fimmu.2018.01098. pmid: 29868036
[27]	Wang Q, Zhang X, Li C, et al. Intracellular Lipid Accumulation Drives the Differentiation of Decidual Polymorphonuclear Myeloid-Derived Suppressor Cells via Arachidonic Acid Metabolism[J]. Front Immunol, 2022, 13:868669. doi: 10.3389/fimmu.2022.868669.
[28]	Ren J, Zeng W, Tian F, et al. Myeloid-derived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells[J]. Am J Reprod Immunol, 2019, 81(4):e13099. doi: 10.1111/aji.13099.
[29]	Zhu W, Tan YQ, Wang FY. Tim-3: An inhibitory immune checkpoint is associated with maternal-fetal tolerance and recurrent spontaneous abortion[J]. Clin Immunol, 2022, 245:109185. doi: 10.1016/j.clim.2022.109185.
[30]	Dimitriadis E, Rolnik DL, Zhou W, et al. Pre-eclampsia[J]. Nat Rev Dis Primers, 2023, 9(1):8. doi: 10.1038/s41572-023-00417-6. pmid: 36797292
[31]	Dong S, Shah NK, He J, et al. The abnormal expression of Tim-3 is involved in the regulation of myeloid-derived suppressor cells and its correlation with preeclampsia[J]. Placenta, 2021, 114:108-114. doi: 10.1016/j.placenta.2021.08.060. pmid: 34509865
[32]	Odobasic D, Hawkins CL, Radic M. Editorial: New roles of neutrophils and granulocytic MDSC in autoimmune diseases, inflammation, and anti-microbial immunity[J]. Front Immunol, 2022, 13:974062. doi: 10.3389/fimmu.2022.974062.
[33]	Giouleka S, Tsakiridis I, Mamopoulos A, et al. Fetal Growth Restriction: A Comprehensive Review of Major Guidelines[J]. Obstet Gynecol Surv, 2023, 78(11):690-708. doi: 10.1097/OGX.0000000000001203. pmid: 38134339
[34]	Shi M, Chen Z, Chen M, et al. Continuous activation of polymorphonuclear myeloid-derived suppressor cells during pregnancy is critical for fetal development[J]. Cell Mol Immunol, 2021, 18(7):1692-1707. doi: 10.1038/s41423-021-00704-w. pmid: 34099889
[35]	Sharif S, Meader N, Oddie SJ, et al. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants[J]. Cochrane Database Syst Rev, 2023, 7(7):CD005496. doi: 10.1002/14651858.CD005496.pub6.
[36]	Lv S, Chen M, Li Z, et al. Blocking OLFM4/galectin-3 axis in placental polymorphonuclear myeloid-derived suppressor cells triggers intestinal inflammation in newborns[J]. Int Immunopharmacol, 2024, 133:112058. doi: 10.1016/j.intimp.2024.112058.
[37]	Ahmadi M, Ali-Hassanzadeh M, Hosseini MS, et al. In vitro-Generated MDSCs Reduce the Pregnancy Complications in an Abortion-Prone Murine Model[J]. Reprod Sci, 2023, 30(4):1217-1228. doi: 10.1007/s43032-022-00995-y.
[38]	Marin NS, Fuente-Muñoz E, Gil-Laborda R, et al. Myeloid-derived suppressor cells as a potential biomarker for recurrent pregnancy loss and recurrent implantation failure: Increased levels of MDSCs in recurrent reproductive failure[J]. Am J Reprod Immunol, 2023, 90(5):e13783. doi: 10.1111/aji.13783.