{"title":"Multi-Layered Mechanisms of Immunological Tolerance at the Maternal-Fetal Interface.","authors":"Jin Soo Joo, Dongeun Lee, Jun Young Hong","doi":"10.4110/in.2024.24.e30","DOIUrl":null,"url":null,"abstract":"<p><p>Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 4","pages":"e30"},"PeriodicalIF":4.3000,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377946/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immune Network","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4110/in.2024.24.e30","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.
妊娠是一个免疫学悖论,母体免疫系统必须耐受表达父源抗体的半异体胎儿。几十年来积累的证据表明,成功妊娠需要积极发展强大的免疫耐受机制。本综述概述了建立胎儿-母体耐受性的多层次过程,包括胎盘的物理屏障、趋化因子介导的白细胞迁移受限、缺乏足够的同种抗原呈递、存在免疫抑制调节性 T 细胞和耐受性蜕膜自然杀伤细胞、免疫检查点分子的表达、赋予免疫逃避功能的特定糖基化模式以及独特的代谢/激素调节。有趣的是,使胎儿产生耐受性的许多策略与癌细胞促进血管生成、侵袭和免疫逃逸的策略相似。因此,进一步阐明胎儿-母体耐受性的机理基础可为开发新型癌症免疫疗法以及了解与耐受性失调过程相关的妊娠并发症的发病机制提供有益的启示。
期刊介绍:
Immune Network publishes novel findings in basic and clinical immunology and aims to provide a medium through which researchers in various fields of immunology can share and connect. The journal focuses on advances and insights into the regulation of the immune system and the immunological mechanisms of various diseases. Research that provides integrated insights into translational immunology is given preference for publication. All submissions are evaluated based on originality, quality, clarity, and brevity