Ozen Maide, Zhao Hui, Lewis David B, Wong Ronald J, Stevenson David K
Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine , Stanford, CA, USA.
Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine , Stanford, CA, USA.
Front Pharmacol. 2015 Apr 24;6:84. doi: 10.3389/fphar.2015.00084. eCollection 2015.
Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity.
正常妊娠是一种免疫耐受状态。许多因素，包括环境、社会经济、遗传以及感染和/或其他炎症原因引起的免疫变化，可能导致个体差异，从而导致正常或病理性妊娠。特别是，免疫系统失衡会导致许多与妊娠相关的疾病，如不孕症、流产、先兆子痫和早产，这些疾病会导致母婴死亡、早产或小于胎龄新生儿。新的研究结果表明，髓系调节细胞和调节性T细胞（Tregs）可能在正常妊娠期间介导免疫耐受。相比之下，效应T细胞（Teffs）被认为会导致不良妊娠结局。此外，母胎耐受会影响发育中的胎儿。研究表明，Treg/Teff平衡会影响产仔数，妊娠诱导的Tregs的过继转移可以防止小鼠的胎儿排斥反应。血红素加氧酶-1（HO-1）通过其抗炎、抗凋亡、抗氧化和抗增殖作用在许多情况下发挥保护作用。HO-1在胎盘中高度表达，在血管生成、胎盘血管发育以及调节妊娠期间的血管张力中发挥作用。此外，HO-1是免疫稳态的主要调节因子，通过介导先天性和适应性免疫系统之间的相互作用。此外，HO-1可以抑制炎症诱导的免疫效应细胞的表型成熟和促炎细胞因子的分泌，并促进抗炎细胞因子的产生。HO-1也可能与T细胞活化有关，并可以通过促进Tregs对效应反应的抑制来限制基于免疫的组织损伤。因此，HO-1及其副产品可能通过其免疫调节作用预防妊娠并发症，对HO-1或其下游效应的调节有可能预防或治疗妊娠并发症和早产。
