母胎界面免疫细胞的代谢调节与妊娠相关并发症的研究进展

doi:10.12280/gjszjk.20220225

摘要/Abstract

摘要：

维持妊娠需要母体免疫细胞与胎儿抗原之间的耐受平衡。母胎界面作为抵抗外来刺激的关键屏障,一直是探讨的热点。母胎界面除了胎盘和子宫之间相互作用,还受到构成蜕膜的母体免疫细胞的叠加调控。母胎免疫界面主要由自然杀伤细胞、巨噬细胞、T细胞和树突状细胞组成,这些细胞共同参与同种异体胎儿的耐受平衡及抗原防御作用。细胞代谢调节是细胞生物学功能的基础,为细胞不断提供着能量。妊娠过程中,为适应内外环境的变化母体代谢调节的速率及方向都随之变化。综述母胎界面免疫细胞的代谢调节,将母胎免疫界面的免疫学及代谢学联系起来,为免疫耐受提供新的见解,也为未来妊娠相关疾病的研究提供新的治疗方向。

关键词: 妊娠, 代谢, 免疫耐受, 杀伤细胞,天然, 巨噬细胞, T淋巴细胞, 树突细胞

Abstract:

Maintenance of pregnancy requires a tolerance balance between maternal immune cells and fetal antigens. The maternal-fetal interface, as a key barrier against external stimuli, has been a hot topic in the field of immunology. In addition to the interaction between placenta and uterus, the maternal-fetal interface is also regulated by the superposition of maternal immune cells that make up the decidua. The maternal-fetal immune interface is mainly composed of natural killer cell, macrophage, T cells and dendritic cells which are involved in the tolerance balance and antigen defense of allogeneic fetus. The regulation of cellular metabolism is the cornerstone of cellular biological function, providing a constant source of energy for cells. During the whole pregnancy, the rate and direction of metabolic regulation were accordingly changed in response to the internal and external environment changes. We discuss the metabolic regulation of immune cells at the maternal-fetal interface in this review by linking immunology and metabolism at the maternal-fetal immune interface, so as to provide new insights into immune tolerance and to offer a new therapeutic direction for future research in pregnancy-related diseases.

Key words: Pregnancy, Metabolism, Immune tolerance, Killer cells, natural, Macrophages, T-lymphocytes, Dendritic cells

张燕, 肖卓妮. 母胎界面免疫细胞的代谢调节与妊娠相关并发症的研究进展[J]. 国际生殖健康/计划生育, 2022, 41(5): 404-408.

ZHANG Yan, XIAO Zhuo-ni. Metabolic Regulation of Immune Cells at the Maternal-Fetal Interface and Related Pregnancy Complications[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(5): 404-408.

参考文献 35

[1]	Xu L, Li Y, Sang Y, et al. Crosstalk Between Trophoblasts and Decidual Immune Cells: The Cornerstone of Maternal-Fetal Immunotolerance[J]. Front Immunol, 2021, 12:642392. doi: 10.3389/fimmu.2021.642392. doi: 10.3389/fimmu.2021.642392 URL
[2]	Loftus RM, Finlay DK. Immunometabolism: Cellular Metabolism Turns Immune Regulator[J]. J Biol Chem, 2016, 291(1):1-10. doi: 10.1074/jbc.R115.693903. doi: 10.1074/jbc.R115.693903 pmid: 26534957
[3]	Rees A, Richards O, Chambers M, et al. Immunometabolic adaptation and immune plasticity in pregnancy and the bi-directional effects of obesity[J]. Clin Exp Immunol, 2022, 208(2):132-146. doi: 10.1093/cei/uxac003. doi: 10.1093/cei/uxac003 URL
[4]	Jia N, Li J. Human Uterine Decidual NK Cells in Women with a History of Early Pregnancy Enhance Angiogenesis and Trophoblast Invasion[J]. Biomed Res Int, 2020, 2020:6247526. doi: 10.1155/2020/6247526. doi: 10.1155/2020/6247526
[5]	Schafer JR, Salzillo TC, Chakravarti N, et al. Education-dependent activation of glycolysis promotes the cytolytic potency of licensed human natural killer cells[J]. J Allergy Clin Immunol, 2019, 143(1):346-358.e6. doi: 10.1016/j.jaci.2018.06.047. doi: S0091-6749(18)31133-3 pmid: 30096390
[6]	Cong J, Wang X, Zheng X, et al. Dysfunction of Natural Killer Cells by FBP1-Induced Inhibition of Glycolysis during Lung Cancer Progression[J]. Cell Metab, 2018, 28(2):243-255.e5. doi: 10.1016/j.cmet.2018.06.021. doi: S1550-4131(18)30443-1 pmid: 30033198
[7]	Martí I Líndez AA, Reith W. Arginine-dependent immune responses[J]. Cell Mol Life Sci, 2021, 78(13):5303-5324. doi: 10.1007/s00018-021-03828-4. doi: 10.1007/s00018-021-03828-4 URL
[8]	Aydin E, Johansson J, Nazir FH, et al. Role of NOX2-Derived Reactive Oxygen Species in NK Cell-Mediated Control of Murine Melanoma Metastasis[J]. Cancer Immunol Res, 2017, 5(9):804-811. doi: 10.1158/2326-6066.CIR-16-0382. doi: 10.1158/2326-6066.CIR-16-0382 pmid: 28760732
[9]	Michelet X, Dyck L, Hogan A, et al. Metabolic reprogramming of natural killer cells in obesity limits antitumor responses[J]. Nat Immunol, 2018, 19(12):1330-1340. doi: 10.1038/s41590-018-0251-7. doi: 10.1038/s41590-018-0251-7 pmid: 30420624
[10]	Zhang T, Shen HH, Qin XY, et al. The metabolic characteristic of decidual immune cells and their unique properties in pregnancy loss[J]. Immunol Rev, 2022, 308(1):168-186. doi: 10.1111/imr.13085. doi: 10.1111/imr.13085 pmid: 35582842
[11]	Yan S, Dong J, Qian C, et al. The mTORC1 Signaling Support Cellular Metabolism to Dictate Decidual NK Cells Function in Early Pregnancy[J]. Front Immunol, 2022, 13:771732. doi: 10.3389/fimmu.2022.771732. doi: 10.3389/fimmu.2022.771732 URL
[12]	Jiang L, Fei H, Jin X, et al. Extracellular Vesicle-Mediated Secretion of HLA-E by Trophoblasts Maintains Pregnancy by Regulating the Metabolism of Decidual NK Cells[J]. Int J Biol Sci, 2021, 17(15):4377-4395. doi: 10.7150/ijbs.63390. doi: 10.7150/ijbs.63390 pmid: 34803505
[13]	Kasture V, Sahay A, Joshi S. Cell death mechanisms and their roles in pregnancy related disorders[J]. Adv Protein Chem Struct Biol, 2021, 126:195-225. doi: 10.1016/bs.apcsb.2021.01.006. doi: 10.1016/bs.apcsb.2021.01.006 pmid: 34090615
[14]	Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease[J]. J Cell Physiol, 2018, 233(9):6425-6440. doi: 10.1002/jcp.26429. doi: 10.1002/jcp.26429 pmid: 29319160
[15]	De Santa F, Vitiello L, Torcinaro A, et al. The Role of Metabolic Remodeling in Macrophage Polarization and Its Effect on Skeletal Muscle Regeneration[J]. Antioxid Redox Signal, 2019, 30(12):1553-1598. doi: 10.1089/ars.2017.7420. doi: 10.1089/ars.2017.7420 URL
[16]	Ma LN, Huang XB, Muyayalo KP, et al. Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?[J]. Front Immunol, 2020, 11:279. doi: 10.3389/fimmu.2020.00279. doi: 10.3389/fimmu.2020.00279 URL
[17]	Tirpe AA, Gulei D, Ciortea SM, et al. Hypoxia: Overview on Hypoxia-Mediated Mechanisms with a Focus on the Role of HIF Genes[J]. Int J Mol Sci, 2019, 20(24):6140. doi: 10.3390/ijms20246140. doi: 10.3390/ijms20246140 URL
[18]	Yang Z, Ming XF. Functions of arginase isoforms in macrophage inflammatory responses: impact on cardiovascular diseases and metabolic disorders[J]. Front Immunol, 2014, 5:533. doi: 10.3389/fimmu.2014.00533. doi: 10.3389/fimmu.2014.00533 pmid: 25386179
[19]	Huang HL, Yang HL, Lai ZZ, et al. Decidual IDO(+) macrophage promotes the proliferation and restricts the apoptosis of trophoblasts[J]. J Reprod Immunol, 2021, 148:103364. doi: 10.1016/j.jri.2021.103364. doi: 10.1016/j.jri.2021.103364 URL
[20]	Gao L, Xu QH, Ma LN, et al. Trophoblast-derived Lactic Acid Orchestrates Decidual Macrophage Differentiation via SRC/LDHA Signaling in Early Pregnancy[J]. Int J Biol Sci, 2022, 18(2):599-616. doi: 10.7150/ijbs.67816. doi: 10.7150/ijbs.67816 pmid: 35002512
[21]	Zhou WJ, Yang HL, Mei J, et al. Fructose-1,6-bisphosphate prevents pregnancy loss by inducing decidual COX-2(+) macrophage differentiation[J]. Sci Adv, 2022, 8(8):eabj2488. doi: 10.1126/sciadv.abj2488. doi: 10.1126/sciadv.abj2488 URL
[22]	Wang W, Sung N, Gilman-Sachs A, et al. T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells[J]. Front Immunol, 2020, 11:2025. doi: 10.3389/fimmu.2020.02025. doi: 10.3389/fimmu.2020.02025 pmid: 32973809
[23]	Sharabi A, Tsokos GC. T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy[J]. Nat Rev Rheumatol, 2020, 16(2):100-112. doi: 10.1038/s41584-019-0356-x. doi: 10.1038/s41584-019-0356-x pmid: 31949287
[24]	Kono M, Yoshida N, Maeda K, et al. Pyruvate dehydrogenase phosphatase catalytic subunit 2 limits Th17 differentiation[J]. Proc Natl Acad Sci U S A, 2018, 115(37):9288-9293. doi: 10.1073/pnas.1805717115. doi: 10.1073/pnas.1805717115 pmid: 30150402
[25]	Fischer K, Hoffmann P, Voelkl S, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells[J]. Blood, 2007, 109(9):3812-3819. doi: 10.1182/blood-2006-07-035972. doi: 10.1182/blood-2006-07-035972 pmid: 17255361
[26]	Bailis W, Shyer JA, Zhao J, et al. Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function[J]. Nature, 2019, 571(7765):403-407. doi: 10.1038/s41586-019-1311-3. doi: 10.1038/s41586-019-1311-3 URL
[27]	Cheng H, Huang Y, Huang G, et al. Effect of the IDO Gene on Pregnancy in Mice with Recurrent Pregnancy Loss[J]. Reprod Sci, 2021, 28(1):52-59. doi: 10.1007/s43032-020-00264-w. doi: 10.1007/s43032-020-00264-w URL
[28]	Daneshmandi S, Cassel T, Higashi RM, et al. 6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function[J]. Elife, 2021, 10:e67476. doi: 10.7554/eLife.67476. doi: 10.7554/eLife.67476 URL
[29]	Daneshmandi S, Cassel T, Lin P, et al. Blockade of 6-phosphogluconate dehydrogenase generates CD8(+) effector T cells with enhanced anti-tumor function[J]. Cell Rep, 2021, 34(10):108831. doi: 10.1016/j.celrep.2021.108831. doi: 10.1016/j.celrep.2021.108831 URL
[30]	Cai F, Jin S, Chen G. The Effect of Lipid Metabolism on CD4(+) T Cells[J]. Mediators Inflamm, 2021, 2021:6634532. doi: 10.1155/2021/6634532. doi: 10.1155/2021/6634532
[31]	Thwe PM, Amiel E. The role of nitric oxide in metabolic regulation of Dendritic cell immune function[J]. Cancer Lett, 2018, 412:236-242. doi: 10.1016/j.canlet.2017.10.032. doi: S0304-3835(17)30669-9 pmid: 29107106
[32]	Wculek SK, Khouili SC, Priego E, et al. Metabolic Control of Dendritic Cell Functions: Digesting Information[J]. Front Immunol, 2019, 10:775. doi: 10.3389/fimmu.2019.00775. doi: 10.3389/fimmu.2019.00775 pmid: 31073300
[33]	Everts B, Amiel E, Huang SC, et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKε supports the anabolic demands of dendritic cell activation[J]. Nat Immunol, 2014, 15(4):323-332. doi: 10.1038/ni.2833. doi: 10.1038/ni.2833 pmid: 24562310
[34]	Mellor AL, Lemos H, Huang L. Indoleamine 2,3-Dioxygenase and Tolerance: Where Are We Now?[J]. Front Immunol, 2017, 8:1360. doi: 10.3389/fimmu.2017.01360. doi: 10.3389/fimmu.2017.01360 pmid: 29163470
[35]	Giovanelli P, Sandoval TA, Cubillos-Ruiz JR. Dendritic Cell Metabolism and Function in Tumors[J]. Trends Immunol, 2019, 40(8):699-718. doi: 10.1016/j.it.2019.06.004. doi: S1471-4906(19)30127-9 pmid: 31301952