摘要
免疫与代谢相互依存、相互协调，它是维持生物体内部稳态的关键机制。在肿瘤免疫学领域，这一主题已成为研究的焦点，并在近年实现了重大突破。然而，在母胎医学中，关于免疫代谢的研究还相对落后。直接研究免疫代谢在子宫内膜微环境中的作用以及调控母胎免疫耐受的报道相对较少。本文综述了目前研究免疫代谢对母胎界面的免疫细胞及其功能实现所需的代谢特征，在缺乏证据和线索的基础上探讨了免疫代谢与妊娠调节之间的相互作用，并试图提出一些新的研究方向和观点。
关键词： 免疫代谢；母胎免疫耐受；母胎界面的免疫细胞
Abstract
Immunity and metabolism are interdependent and coordinated, which is the key mechanism to maintain the homeostasis of the organism. In the field of tumor immunology, this topic has become the focus of research and has achieved major breakthroughs in recent years. However, in maternal-fetal medicine, the research on immune metabolism is still relatively backward. There are relatively few reports on the role of immune metabolism in endometrial microenvironment and the regulation of maternal and fetal immune tolerance. In this paper, we reviewed the metabolic characteristics of immune metabolism on the mother-fetal interface of immune cells and their functional realization, discussed the interaction between immune metabolism and pregnancy regulation on the basis of lack of evidence and clues, and tried to put forward some new research directions and viewpoints.
Key words： Immune metabolism; Maternal fetal immune tolerance; Immune cells at the mother-fetal interface
参考文献 References
[1] Moffett ALoke C. Immunology of Placentation in Eutherian Mammals. Nat Rev Immunol (2006) 6:584–94.
[2] Cha JSun XDey SK. Mechanisms of Implantation: Strategies for Successful Pregnancy. Nat Med (2012) 18:1754–67.
[3] PrabhuDas MBonney ECaron KDey SErlebacher AFazleabas A, et al. Immune Mechanisms at the Maternal-Fetal Interface: Perspectives and Challenges. Nat Immunol (2015) 16:328–34.
[4] Newton ERMay L. Adaptation of Maternal-Fetal Physiology to Exercise in Pregnancy: The Basis of Guidelines for Physical Activity in Pregnancy. ClinMed Insights Womens Health (2017) 10.
[5] O’Neill LAJPearce EJ. Immunometabolism Governs Dendritic Cell and Macrophage Function. J Exp Med (2016) 213:15–23.
[6] Ip WKEHoshi NShouval DSSnapper SMedzhitov R. Anti-Inflammatory Effect of IL-10 Mediated by Metabolic Reprogramming of Macrophages. Science (2017) 356:513–9.
[7] Kabat AMPearce EJ. Inflammation by Way of Macrophage Metabolism. Science (2017) 356:488–9.
[8] Gellersen BBrosens JJ. Cyclic Decidualization of the Human Endometrium in Reproductive Health and Failure. Endocrine Rev (2014) 35:851–905.
[9] Schumacher ASharkey DJRobertson SAZenclussen AC. Immune Cells at the Fetomaternal Interface: How the Microenvironment Modulates ImmuneCells To Foster Fetal Development. JI (2018) 201:325–34.
[10] Thiele KDiao LArck PC. Immunometabolism, Pregnancy, and Nutrition. Semin Immunopathol (2018) 40:157–74.
[11] Bulmer JNWilliams PJLash GE. Immune Cells in the Placental Bed. Int J Dev Biol (2010) 54:281–94.
[12] Moffett-King A. Natural Killer Cells and Pregnancy. Nat Rev Immunol (2002) 2:656–63.
[13] Cartwright JEJames-Allan LBuckley RJWallace AE. The Role of Decidual NK Cells in Pregnancies With Impaired Vascular Remodelling. J Reprod Immunol (2017) 119:81–4.
[14] Slattery KWoods EZaiatz-Bittencourt VMarks SChew SConroy M, et al. Tgfb Drives NK Cell Metabolic Dysfunction in Human Metastatic Breast Cancer. J Immunother Cancer (2021) 9(2):e002044.
[15] Donnelly RPLoftus RMKeating SELiou KTBiron CAGardiner CM, et al. Mtorc1-Dependent Metabolic Reprogramming is a Prerequisite for NK Cell Effector Function. J Immunol (2014) 193:4477–84.
[16] Keating SEZaiatz-Bittencourt VLoftus RMKeane CBrennan KFinlay DK, et al. Metabolic Reprogramming Supports IFN-g Production by CD56bright NK Cells. J Immunol (2016) 196:2552–60.
[17] Zheng XQian YFu BJiao DJiang YChen P, et al. Mitochondrial Fragmentation Limits NK Cell-Based Tumor Immunosurveillance. Nat Immunol (2019) 20:1656 –67.
[18] Assmann NO’Brien KLDonnelly RPDyck LZaiatz-Bittencourt VLoftus RM, et al. Srebp-Controlled Glucose Metabolism is Essential for NK Cell Functional Responses. Nat Immunol (2017) 18:1197–206.
[19] Kidani YElsaesser HHock MBVergnes LWilliams KJArgus JP, et al. Sterol Regulatory Element–Binding Proteins are Essential for the Metabolic Programming of Effector T Cells and Adaptive Immunity. Nat Immunol (2013) 14:489–99.
[20] Michelet XDyck LHogan ALoftus RMDuquette DWei K, et al. Metabolic Reprogramming of Natural Killer Cells in Obesity Limits Antitumor Responses. Nat Immunol (2018) 19:1330–40.
[21] Loftus RMAssmann NKedia-Mehta NO’Brien KLGarcia AGillespie C, et al. Amino Acid-Dependent Cmyc Expression is Essential for NK Cell Metabolic and Functional Responses in Mice. Nat Commun (2018) 9:2341.
[22] Williams PJSearle RFRobson SCInnes BABulmer JN. Decidual Leucocyte Populations in Early to Late Gestation Normal Human Pregnancy. J Reprod Immunol (2009) 82:24–31.
[23] Murray PJ. Macrophage Polarization. Annu Rev Physiol (2017) 79:541–66.